The Supreme Court (SC) of India's judgment on March 11, 2026, in Harish Rana vs Union of India brought greater clarity on the complex issue of end-of-life decisions; specifically on withdrawal of care from persons in a "permanent vegetative state" [1]. In an earlier landmark judgment in Aruna Shanbaug vs Union of India in 2011, the Court had allowed petitions in favour of "withholding or withdrawal of life support" to allow "a dignified death", in very rare cases, following specific procedures outlined in that judgment [2]. In 2018, in Common Cause vs Union of India, the SC recognised the "right to die with dignity" as an extension of the fundamental "right to live with dignity" under Article 21 of the Indian Constitution. Patients who were terminally ill could refuse futile or burdensome treatment and could register Advance Directives, against unnecessary suffering caused by such treatment [3]. That judgment detailed the decision-making process to be followed for withdrawal of treatment, in order to protect vulnerable patients and prevent misuse. These procedural steps were later simplified by the SC in 2023 into what is termed "Common Cause Guidelines 2023" [4].
Reconstruction of distal radius defects following oncological resection remains technically challenging. Free fibula flap (FFF) arthrodesis offers a biological and durable reconstructive option; however, reports remain limited. We retrospectively reviewed 8 patients who underwent en bloc resection of Campanacci grade III giant cell tumors (2017-2024) of the distal radius, followed by reconstruction with FFF arthrodesis. Clinical, radiological, and functional outcomes were analyzed, including union, recurrence, complications, donor-site morbidity, and Musculoskeletal Tumor Society, Disabilities of the Arm, Shoulder, and Hand (DASH), and visual analog scale scores. All patients achieved radiographic union (mean 7 mo proximally, 11 mo distally). Median follow-up was 36 months. Seven (87.5%) patients remained disease-free; 1 patient developed multicentric soft-tissue local recurrence with pulmonary metastases, which was managed surgically along with radiotherapy and medical treatment. The patient remained disease-free at last follow-up. Mean Musculoskeletal Tumor Society score was 24.5, DASH score was 20.3, and visual analog scale score was 2.3, indicating satisfactory limb function and minimal pain. Donor-site morbidity was minimal. FFF arthrodesis maintained viability even after postoperative fractures, soft-tissue recurrences, and adjuvant therapy, underscoring its robustness. It represents a valuable microsurgical option when long-term stability and biological incorporation are prioritized.
Shigella is a leading cause of childhood diarrhea in low- and middle-income countries and is increasingly resistant to first-line antibiotics. We conducted a surveillance study to determine the incidence, genomic characteristics, and AMR profiles of Shigella infections in children under five with moderate to severe diarrhea (MSD) in Lusaka, Zambia. Between 15 September 2020 and 30 November 2021, a prospective cohort study of 1,400 children under five was enrolled during a community census in a peri-urban setting and passively followed for 9.5 months for MSD. During enrollment, socio-demographic data were collected using electronic questionnaires, while clinical data were collected through the DHIS platform. The main outcome, Shigella in diarrheal stool in under 5 children, was detected using culture and Loop-mediated Isothermal Amplification (LAMP) targeting the ipaH gene. Cox proportional hazards models were used to assess the incidence and risk factors of Shigella (ipaH) infections. Whole-genome sequencing (WGS) was used to characterize the genomic diversity and antimicrobial resistance genes, complemented by phenotypic antibiotic susceptibility testing. There were 230 first episodes of Shigella over a follow-up time of 9,581.7 child-months, yielding an incidence of 24.0 (95% CI 21.1-27.3) cases per 1,000 child-months, with the highest incidence among 2 to 3-year-olds. The key risk factors identified were the water source (p=0.025) and age group (p=0.014). Genotypic characterization revealed 10 S. flexneri , 9 S. sonnei , and 3 S. boydii . The S. sonnei isolates formed two clusters, differing in virulence factors and plasmid profiles, indicating two possible circulating strains. Shigella isolates exhibited phenotypic and genotypic multidrug resistance, including against trimethoprim, aminoglycosides, and beta-lactams. Plasmid-mediated quinolone resistance (qnrS1) was identified in four S. flexneri isolates, with these genes located on the IncFIB(K) plasmid, highlighting the potential for horizontal transmission and spread of quinolone resistance in this region. No phenotypic and genotypic resistance to macrolides, the first-line treatment for Shigella in Zambia, was observed. We report a high burden of Shigella with multidrug resistance, including resistance to fluoroquinolones. These findings highlight the increasing resistance of Shigella to first-line antibiotics and underscore the importance of developing safe and effective vaccines, improving WASH conditions, and ongoing AMR surveillance. The EDCTP2 program, supported by the European Union, the Faculty for the Future Foundation (FFTF), the Netherlands Organization for Health Research and Development (ZonMw), and Health-Holland AMR-Global, Gloria, and Track-AMR. Evidence before this study: Despite Shigella being a leading cause of bacterial diarrheal mortality globally, there is a critical lack of up-to-date data on its burden and associated antimicrobial resistance (AMR) in high-risk settings, such as sub-Saharan Africa (SSA). We searched PubMed for studies published between 2000 and May 2025, using the terms " Shigella ," "antimicrobial resistance," and "sub-Saharan Africa." Only three studies (GEMS, MAL-ED, VIDA) involving extensive surveillance in SSA countries were identified, all conducted before 2018. None integrated disease burden, genomic characterization of circulating strains, and both phenotypic and genotypic AMR profiling. In Zambia, we found no published surveillance data on Shigella or resistance patterns in children. The added value of the study: We present an up-to-date, integrated assessment of the burden, genomic diversity, and AMR profiles among Shigella isolates in children under five in SSA, specifically in a high-risk peri-urban setting in Lusaka, Zambia. By prospectively following a large cohort of 1,400 children and combining culture with WGS, we provide detailed insights into the disease burden and epidemiology of circulating Shigella strains and the relevance of candidate vaccine antigens. We reveal a high prevalence of multidrug resistance (MDR), including plasmid-mediated and phenotypic resistance to ciprofloxacin, the first-line treatment for Shigella . We further complement genotypic AMR with phenotypic AMR testing to predict potential resistance genes while measuring antibiotic susceptibility in real clinical settings. Implications of all the available evidence: We demonstrate that Shigella is genomically diverse and an important etiology of moderate to severe gastroenteritis in Zambian children. Risk factors include increasing age and poor WASH. We observed plasmid-mediated resistance to ciprofloxacin and MDR, which threatens the efficacy of current Shigella treatment and risks population-level AMR spread. These results highlight the need for improved WASH, antibiotic stewardship, and the development of effective vaccines, supported by ongoing genomic surveillance, to facilitate disease monitoring, inform treatment guidelines, guide vaccine antigen selection, and inform evidence-based antibiotic stewardship.
Data deficiency is a substantial challenge for extinction risk assessments because incomplete data means we cannot accurately identify priority protected areas for conservation. Here, we use the International Union for Conservation of Nature (IUCN) distributions of amphibians, sharks and rays, fish, mammals, birds, and reptiles to identify hotspots of data deficient species. We found that areas with high numbers of data deficient species were not randomly distributed and did not necessarily overlap with hotspots of biodiversity, particularly in the Amazon and West Africa. Data deficiency hotspots were concentrated around tropical South America, Africa, and Southeast Asia; however, this distribution varied between taxa. Hotspots of data deficient amphibians were concentrated around the tropical Andean forests of Colombia, Peru, and Ecuador; throughout Brazil; and in the New Guinea Highlands. The tropical forests of the Congo River basin, Papua New Guinea, and the Philippines were hotspots for avian data deficiency. Data deficient chondrichthyans were concentrated in the tropical seas, particularly around the western coast of Africa, East Asia, and the tropical Americas. Indochina was identified as the primary hotspot for data deficient freshwater fish, whereas the Indo-Pacific was the primary hotspot for data deficient marine fish. Data deficient marine mammals were broadly distributed around the southern oceans, South America, Southeast Asia, and Northwest Africa. Data deficient herpetofauna were concentrated around tropical Asia, whereas tropical South America, Indonesia, and central Africa were the hotspots for data deficient terrestrial mammals. Although data deficiency reflected drivers of biodiversity more broadly (e.g., latitude), other factors were also influential, including the amount of conservation funding invested by a country and population density. Increasing evidence suggests that data deficient species are disproportionately likely to be threatened with extinction. Scientists urgently need to focus their research efforts on these data deficiency hotspots and ensure protected area networks are suitably representative and include data deficient species. Furthermore, the accuracy of status assessments needs to be ascertained, and data deficient species need to be prioritized for study to ensure they are not lost before they are identified. Identificación de puntos calientes de deficiencia de datos faunísticos para dirigir la investigación y el monitoreo urgentes Resumen La falta de datos es un reto importante para las evaluaciones del riesgo de extinción, ya que la información incompleta nos impide identificar con precisión las áreas protegidas prioritarias para la conservación. En este estudio, utilizamos los datos de distribución de la Unión Internacional para la Conservación de la Naturaleza (UICN) sobre anfibios, tiburones y rayas, peces, mamíferos, aves y reptiles para identificar los puntos críticos de especies con datos insuficientes. Descubrimos que las áreas con un elevado número de especies con datos insuficientes no se distribuían de forma aleatoria y no se solapaban necesariamente con los puntos calientes de biodiversidad, especialmente en la Amazonía y África Occidental. Los puntos calientes de especies con datos insuficientes se concentraban en torno a las zonas tropicales de Sudamérica, África y el sudeste asiático; sin embargo, esta distribución variaba entre los taxones. Los puntos calientes de anfibios con datos insuficientes se concentraban en torno a los bosques tropicales andinos de Colombia, Perú y Ecuador; en todo Brasil; y en las tierras altas de Nueva Guinea. Los bosques tropicales de la cuenca del río Congo, Papúa Nueva Guinea y Filipinas eran puntos calientes para las aves con datos insuficientes. Los condrictios con datos insuficientes se concentraban en los mares tropicales, especialmente en torno a la costa occidental de África, el este de Asia y las zonas tropicales de América. Se identificó Indochina como el principal punto caliente para los peces de agua dulce con datos insuficientes, mientras que el Indo‐Pacífico era el principal punto caliente para los peces marinos con datos insuficientes. Los mamíferos marinos con datos insuficientes se distribuían ampliamente por los océanos del sur, Sudamérica, el sudeste asiático y el noroeste de África. La herpetofauna con datos insuficientes se concentraba en la zona tropical de Asia, mientras que la zona tropical de Sudamérica, Indonesia y África central eran los puntos calientes para los mamíferos terrestres con datos insuficientes. Si bien la falta de datos reflejaba factores que influyen en la biodiversidad de manera más general (por ejemplo, la latitud), también influían otros factores, como la cantidad de fondos destinados a la conservación por parte de un país y la densidad de población. Cada vez hay más indicios de que las especies con datos insuficientes tienen una probabilidad desproporcionadamente mayor de estar en peligro de extinción. Los científicos deben centrar urgentemente sus esfuerzos de investigación en estos puntos calientes de falta de datos y garantizar que las redes de áreas protegidas sean adecuadamente representativas e incluyan a las especies con datos insuficientes. Además, es necesario verificar la precisión de las evaluaciones de estado, y se debe dar prioridad al estudio de las especies con datos insuficientes para garantizar que no se pierdan antes de ser identificadas.
Anti-amyloid immunotherapies in Alzheimer's disease (AD) are newly authorized for use in the European Union (AD). In a national online survey in 2024, we aimed to assess French practitioners' opinion and knowledge regarding indications and risk management plan. Answers were based on clinical trial criteria. On 303 practitioners, most knew general indications except 19.1% who considered prescribing without AD biomarkers. Side effects were correctly identified, but specific knowledge on amyloid-related imaging abnormalities was lacking. Tertiary memory clinic practitioners had better knowledge on indications (p < 0.001) and side effects (p = 0.033).
Stereotactic ablative radiotherapy (SABR) is increasingly administered in hepatocellular carcinoma (HCC) treatment. The CyberKnife (CK) system is the most advanced robotic radiosurgery system for delivering SABR. Using three-dimensional multi-angle irradiation, a unique fiducial marker, and a synchronous respiratory tracking system, the off-target caused by respiratory movement is maximally avoided, which achieves favorable dose conformation, and the dose rapidly drops off in the surrounding normal tissue. In a real sense, CK achieves accurate positioning, planning, and irritation. The Chinese expert consensus on CK for HCC was established after discussion.
Glioma is the most common and highly aggressive tumor of the central nervous system. Increasing evidence indicates that metabolic reprogramming and the tumor immune microenvironment are intricately interconnected and jointly contribute to tumor initiation, progression, and therapeutic resistance. In recent years, advances in multi-omics technologies have revealed that multiple metabolic pathways-including nucleotide, amino acid, and lipid metabolism-are closely associated with immune cell infiltration, immune evasion, and clinical outcomes in glioma, leading to the emergence of the "metabolic-immune axis" concept. This review systematically summarizes the regulatory mechanisms by which metabolic reprogramming shapes the glioma immune microenvironment and highlights key metabolic genes and immune phenotypes as potential molecular biomarkers for prognosis prediction and immunotherapeutic response. We further discuss multi-omics-based glioma classification strategies, the mechanistic roles of metabolic pathways in immune escape, and the therapeutic potential of combining metabolic-targeted interventions with immunotherapy. By integrating current research advances and existing challenges, this review aims to provide a comprehensive framework for understanding the metabolic-immune interplay in glioma and to identify promising targets for precision therapy and future clinical translation.
Not available.
Urbanization-driven, large-scale rural-to-urban migration in China has substantially modernized household energy use and reshaped air pollution exposure pathways. However, the magnitude, underlying drivers, and temporal evolution of the resulting health outcomes from combined indoor and outdoor air pollution remain insufficiently resolved. Here, by coupling a reconstruction of seven decades of migration (1949-2021) with nationwide household energy surveys, we quantify migration-attributable changes in integrated (indoor + outdoor) PM2.5 exposure and mortality. Relative to a no-migration counterfactual from 1949 onward, migration reduced integrated PM2.5 exposure by 27.6 μg·m-3 (15.7-39.4 as the 95% confidence interval) in 2019 and cumulatively avoided 2.3 (1.9-2.6) million deaths since 1949, with reductions in indoor exposure providing the dominant contribution. Arising from rural-urban disparities in household energy use, these health gains were pronounced even during intermediate stages of societal development and are likely to occur in other transitioning economies worldwide. Our study thus challenges the conventional view that rapid urbanization in developing economies is strictly detrimental to environmental health.
Pronation of first metatarsal (M1) in hallux valgus (HV) is currently the subject of a growing body of scientific research. Several methods of manual measurements have been developed, providing heterogeneous results. Our objective was to develop automatic 3D weightbearing computed tomography (WBCT) measurements in a retrospective case-control design to compare coronal rotation of M1 head relative to the ground, M1 intrinsic torsion, and valgus deviation of M1 distal articular surface (or distal metatarsal articular angle [DMAA]) in HV and controls. Forty-four symptomatic HV and 44 matched controls were retrospectively enrolled, all of whom had undergone WBCT acquisition. Bone segmentation was performed (Bonelogic 2.1 software). Two methods were developed to assess position of the M1 head. One was based on automatic geometric fitting of a cylinder on the head, and the other on automatic selection of the position of the sesamoid gutters. Similarly, 2 methods were developed to assess the position of the M1 base. One was defined using principal components analysis (PCA) of the proximal articular surface of M1, and the other using the longest diagonal of the M1 base. First metatarsal head rotation relative to the ground was, respectively, 8.9° ± 8.4° (95% CI 6.1°-11.7°) and 2.1° ± 6.4° (95% CI 0.1°-4.1°) via the cylinder method (P < .001) and 9° ± 8.3° (95% CI 6.2°-11.8°) and 0.7° ± 6.8° (95% CI -1.4° to 2.8°) via the gutters method (P < .001) in the HV and control groups. Combining the different sets of head and base measurements, the increase in M1 intrinsic torsion in HV ranged from 2° to 5°. The DMAA was 11.4° ± 6.9° (95% CI 9.3°-13.5°) in the HV group and 5.6° ± 4.7° (95% CI 4.1°-7.0°) in the control group (P < .001). Using automatic 3D WBCT measurements, we found that HV showed an increase in M1 head pronation relative to the ground of 7° to 8° greater than controls, with an increase in M1 intrinsic torsion in pronation of 2° to 5° and an increase in valgus deviation of the M1 distal articular surface of approximately 6°. Changing measurements reference points altered angular values in our study, particularly when moving from measurements based on the sesamoid gutters to gutter-independent measurements, highlighting that these methods may capture different anatomic constructs. Level III, case control study.
Immune escape remains a major barrier to durable cancer immunotherapy. Although checkpoint blockade has transformed cancer treatment, resistance commonly reflects broader tumor-intrinsic and microenvironmental programs that sustain immune dysfunction. At this interface, STAT3 emerges as a central organizing node. Beyond its canonical role in inflammatory and oncogenic signaling, STAT3 links tumor cell plasticity, immune suppression, and metabolic adaptation across the tumor ecosystem. In tumor cells, STAT3 promotes stemness, survival, checkpoint ligand expression, impaired antigen presentation, and immunosuppressive secretomes. In immune compartments, it drives regulatory T cell expansion, myeloid-derived suppressor cell accumulation, tumor-associated macrophage polarization, and dendritic cell dysfunction, thereby stabilizing an immune-resistant niche. STAT3 also reinforces immune escape through metabolic rewiring and multicellular feed-forward circuits. These features make STAT3 an attractive but challenging therapeutic target. Here, we discuss how STAT3 functions at the tumor-immune interface to coordinate immune escape and highlight therapeutic opportunities for targeting this axis in cancer.
The clinical impact of changes in the bifurcation angle throughout the cardiac cycle (BAC) after percutaneous coronary intervention (PCI) for left main coronary bifurcation lesions (LMCBLs) remains controversial, and the associated long-term evolution post-stenting remains unknown. Therefore, this study aimed to evaluate temporal changes in the BAC and the related impact on lesion progression in patients undergoing single- or dual-stenting. Proximal (PBAC) and distal (DBAC) bifurcation angles were quantified throughout the cardiac cycle using two-dimensional quantitative coronary angiography at optimal views before the procedure, immediately after, and at long-term follow-up. These measurements represented the absolute difference between the end-diastolic and end-systolic angles for the left main (LM) to the left circumflex (LCX) and for the left anterior descending (LAD) to the LCX. Lesion progression was assessed from increases in diameter stenosis percentage (iDS%) from post-procedure to follow-up. A total of 284 patients underwent single-stenting (LM-LAD), and 84 underwent dual stenting (LM-LAD-LCX). Changes in the PBAC were unaffected by interventional strategies or time. The DBAC was narrowed post-stenting in all patients, but rebounded to pre-procedural levels during follow-up in the single-stenting group. In contrast, the DBAC remained at post-procedural levels in the dual-stenting group. Lesion progression was more pronounced in patients with dual stenting, particularly in the LCX. The pre-procedural PBAC correlated linearly with the iDS%-LCX metric in the dual stenting. The PBAC remained stable over time and across strategies, whereas the DBAC decreased post-stenting. During follow-up, the DBAC rebounded in the single-stenting group but remained low in the dual-stenting group. The pre-procedural PBAC represents an independent anatomical risk marker for future LCX progression in patients with dual-stented LMCBLs.
Childhood overweight/obesity (Ov/Ob), and its association with metabolic complications, known as metabolically unhealthy obesity (MUO), is a major public health problem. Diet is an important modifiable determinant of weight status, but the relationship between dietary patterns and Ov/Ob or MUO in children/adolescents in Western countries remains poorly studied. This systematic review and meta-analysis aimed to explore associations between adherence to dietary patterns and Ov/Ob or MUO risk in children/adolescents aged 2-19 years. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to identify prospective epidemiological studies and randomized controlled trials (RCTs), with ≥12 months of follow-up for both study designs, from PUBMED and Scopus published between January 2013 and November 2024. Thirty-two prospective studies were included, all of which reported on Ov/Ob risk. No studies addressing MUO risk were identified. Nineteen studies were included in the meta-analysis. The dietary patterns were categorized as healthy or unhealthy. Healthy dietary patterns had a positive effect, whereas unhealthy dietary patterns had a negative impact on various anthropometric parameters in children and adolescents. A higher level of adherence to a healthy dietary pattern was associated with lower odds of childhood Ov/Ob (odds ratio [OR], 0.86; 95% CI, 0.77-0.96 [adjusted model]) and with a decrease in the longitudinal change of the body mass index (β, -.10; 95% CI, -.0.16 to -.0.05 kg/m2 [adjusted model]) while a higher level of adherence to an unhealthy dietary pattern was associated with higher odds of childhood Ov/Ob (OR, 1.22; 95% CI, 1.08-1.37 [adjusted model]) compared to a lower level of adherence. In children and adolescents, a preventive effect against Ov/Ob is exhibited with higher adherence to healthy dietary patterns, while unhealthy dietary patterns contribute to an increased risk of Ov/Ob. The observed associations were modest in magnitude, and the absence of RCTs limits the strength of the evidence. No studies were identified relative to MUO, highlighting a significant research gap. PROSPERO registration No. [CRD42023477613].
The thymus provides a specialized microenvironment for T cell development and selection, yet the cellular heterogeneity and molecular dynamics that govern human prenatal thymopoiesis remain incompletely characterized. We constructed an integrative single-cell atlas of human prenatal thymocytes from 7 to 23 post-conception weeks by combining five published datasets. Selection intermediates were classified based on coreceptor expression patterns. Pseudotime analysis, regulon profiling, metabolic analysis, and cell-cell communication modeling were applied to characterize developmental dynamics. We identified three transitional populations, Sel. int. DP, Sel. int. CD4, and Sel. int. CD8, positioned between DP and single-positive stages. Critically, our findings reveal that CD4/CD8 lineage commitment in the developing human thymus is not a single event, but an asymmetric, multi-stage dynamic process. This asymmetry manifests in three distinct dimensions. First, at the signaling level, Sel. int. CD4 cells exhibit enriched TCR and cytokine signaling activities compared to their Sel. int. CD8 counterparts. Second, at the temporal level, CD4 lineage traits emerge coincident with cellular activation, whereas CD8 lineage characteristics appear only after activation subsides. Third, at the microenvironmental level, Sel. int. CD8 and CD8+ T cells display the most extensive interaction networks with thymic stromal cells. Pseudotime analysis delineated two developmental paths branching at the Sel. int. DP stage toward the CD4+ and CD8+ lineages, revealing four distinct gene expression patterns encompassing activation, viral response, differentiation, and apoptotic programs. Collectively, this atlas provides a comprehensive resource for understanding the asymmetric, multi-stage dynamics of human prenatal T cell development and the cellular crosstalk that orchestrates CD4/CD8 lineage commitment.
To evaluate the technical feasibility, short-term safety, and clinical outcomes of an incomplete osteotomy at the femoral insertion of the lateral collateral ligament (LCL) for expanding a tight lateral compartment during arthroscopic lateral meniscus repair. A single-institution retrospective case series was conducted in patients with lateral meniscus tears and a tight lateral compartment who underwent LCL femoral insertion osteotomy between January 2020 and December 2022. Osteotomy was performed only when standard exposure maneuvers, including the figure-four position, portal adjustment, and gentle varus stress, failed to provide safe visualization and instrument access. The primary outcome was technical success, defined as adequate arthroscopic exposure and completion of the planned meniscal repair. Secondary outcomes included Lysholm score, International Knee Documentation Committee (IKDC) score, Visual Analog Scale (VAS) score for knee pain, osteotomy healing on computed tomography (CT), meniscal healing on magnetic resonance imaging (MRI), and complications. Twenty-five knees were included and followed for 12 months. Adequate exposure of the lateral meniscus and completion of meniscal repair were achieved in all cases. At 12 months, Lysholm, IKDC, and VAS scores improved significantly compared with preoperative values (all P < 0.001). CT at 3 months showed satisfactory osteotomy healing without displacement in all patients. MRI at 12 months demonstrated meniscal healing in 19 patients (76%); the 6 patients who did not meet MRI healing criteria were asymptomatic and did not require reoperation during follow-up. No infection, neurovascular complication, clinically apparent varus instability, loss of reduction, or serious complication was observed. In selected patients with lateral meniscus tears and a tight lateral compartment, arthroscopic repair combined with incomplete osteotomy of the LCL femoral insertion may facilitate exposure and meniscal repair with satisfactory short-term functional recovery. Because this retrospective case series lacked a control group and objective quantification of joint-space widening, the findings should be confirmed in prospective comparative studies with longer follow-up.
Precise control over cation distribution is critical for high-performance perovskite solar cells (PSCs). Conventional bulk doping often leads to vertical segregation and lattice strain, while surface passivation dose not ensure bulk homogeneity. We introduce a triple-alkali interlayer (LiOH/KCl/CsI) deposited on the electron transport layer prior to crystallization of the perovskite film. This design spatially decouples crystallization regulation from compositional modulation, i.e., localized Li+ and K+ ions reconstruct the buried contact and passivate defects and interfacial Cs+ acts as a dynamic source for in situ upward diffusion. This bottom-up mechanism facilitates stress-free crystallization, resulting in a dense, preferentially oriented perovskite film with a void-free buried interface and superior compositional homogeneity. Consequently, the resulting champion n-i-p PSC achieves a remarkable power conversion efficiency of 26.13%, with a high open-circuit voltage of 1.184 V and a fill factor of 83.81%. Furthermore, the devices demonstrate robust durability maintaining 93.7% after 1440 h of continuous 1-sun irradiation at 65°C. This work provides a promising pathway for managing cation dynamics to realize efficient and stable perovskite photovoltaics.
Alterations in lived time and space mark many mental disorders, yet they unfold in different ways. In schizophrenia spectrum disorders (SSD), the core disturbance lies at the microstructural level: fragmented temporal synthesis and disintegration of world, self, and body. In contrast, both mood disorders (MOD) and SSD involve more accessible macro-level shifts, such as acceleration or slowing of the passage of time, fixation on the past, or blockage of the future, difficulties in social space. This overlap raises the question of how such similarities in time and space experiences of SSD and MOD can occur while, at the same time, distinguishing them. To address this question, we used data from 26 SSD and 26 MOD patients, derived from phenomenological interviews based on the Scale for Time and Space Experience in Psychosis (STEP). We compared groups on the total STEP score and its time and space subscales, and examined differences across the 25 individual items. In a second step, we subdivided the SSD group into high and low temporospatial disturbance groups to further probe distinctions and overlaps. The results confirm that SSD is characterized by fragmentation of temporal experience, including diminished synthesis and changes in anisotropy, fragmentation of world, self, and body. Shared items between MOD and SSD involved changes in the speed of time, shifts away from future orientation toward past and present, and spatial items related to distance and social interaction. Taken together, the findings indicate commonalities across disorders and disturbances that remain more characteristic of SSD.
Graphical AbstractFor image description, please refer to the figure legend and surrounding text.
Tooth morphogenesis in mice provides valuable insights into the cellular and molecular mechanisms governing organ shape. During the critical transition from the dental placode to the early cap stage (E12.5-E14.5), epithelial invagination and shape changes are accompanied by complex cellular rearrangements, including suprabasal intercalation and collective cell behaviors. This study examined how Syndecan-4 (Sdc4), focal adhesion kinase (FAK), and basement membrane-related interactions are deployed during early mandibular first molar development. We performed a stage-matched reanalysis of publicly available single-cell RNA-seq datasets, together with morphometric and spatial validation, to characterize epithelial state changes across E12.5-E14.5. At E12.5, DE-like epithelial cells displayed a proliferative odontogenic program enriched for cell-cycle regulators and key signaling pathways, including Wnt and Hippo. By E13.5, extracellular matrix components, including collagen, laminin, and agrin, together with focal adhesion-related pathways, became prominent in association with epithelial remodeling. At E14.5, upregulation of adhesion and structural scaffold components was consistent with tissue stabilization during morphogenesis. Across these stages, the data suggest a temporal shift from proliferative odontogenic activity to ECM-adhesion remodeling and then to tissue stabilization during early molar morphogenesis. Integrating the transcriptomic, morphometric, and spatial findings, we propose that an ECM-Sdc4-FAK-related signaling axis may contribute to epithelial invagination and the emergence of buccolingual asymmetry. More broadly, these findings highlight cell-matrix interactions as an important component of the early tooth morphogenetic environment, while functional perturbation studies will be needed to establish direct causality.
Perilla frutescens (L.) Britton is a highly valuable medicinal plant known for a wide variety of chemotypes based on the components of its essential oils. The appropriate and secure medicinal use of P. frutescens has been severely limited due to the lack of chemotype classification standards and pharmacological studies. In this paper, a classification standard for essential oils in P. frutescens was proposed. The pharmacological activities of different chemotypes or their main components were summarized. Genetic and molecular studies related to the formation of different chemotypes were also reviewed. The molecular mechanism underlying the formation of P. frutescens chemotypes is also discussed to pave the way for the innovation of P. frutescens germplasms for medicinal use.