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Lay sources contend that the narcissistic abuse cycle occurs in many relationships and inflicts serious psychological harm. However, the phenomenon has scant mention in academic literature. Researchers should refine its definition, boundaries, characteristics, and management. Clinicians should be vigilant about its presence and employ interventions proven effective in similar conditions.
Non-cirrhotic portal vein thrombosis (PVT) is a rare but dangerous illness with few studies on risk factors and outcomes. This study sought to evaluate the clinical characteristics, risk factors, anticoagulation response, and consequences of non-cirrhotic PVT in hospitalized patients. We performed a retrospective study on 47 hospitalized patients with suspected non-cirrhotic PVT. Clinical, laboratory, and radiographic data were gathered. Descriptive statistics were employed to describe baseline attributes. The associations between risk factors and outcomes (thrombus resolution, intestinal ischemia, portal hypertension, and mortality) were examined using chi-square, Fisher's exact, Mann-Whitney U, and Kruskal-Wallis tests, if needed. Around 95.7% of patients (45/47) had radiologically verified non-cirrhotic PVT. The average age was 49.4 years (SD 19.5), and 61.7% were female. Obesity (BMI ≥30) was reported in 42.6%. Prothrombotic diseases were found in 17.0%, cancer in 25.5%, and a recent infection in 42.6%. Complete thrombus resolution occurred in 29.8% of cases, with no significant difference across anticoagulation methods (low molecular weight heparin (LMWH) 36.0%, direct oral anticoagulants (DOACs) 16.7%, and warfarin 50.0%; p=0.448). Bowel ischemia was substantially linked to recent infection (p = 0.016). The 90-day mortality rate was 17.0%. Significant univariate predictors of 90-day death were malignancy (p < 0.001), recent infection (p = 0.009), LMWH use (p = 0.018), and longer hospital stay (p = 0.041). There were no deaths among patients who received DOACs or warfarin. Non-cirrhotic PVT poses a significant mortality risk. Recent infection and underlying malignancy are strong indicators of negative outcomes. The link between anticoagulant type and mortality deserves additional exploration in prospective trials.
Skin-to-skin contact for pain (SSCP) has been recommended as a pain management strategy broadly for infants but no systematic reviews have focused exclusively on the youngest of preterm infants. These infants are subjected to increased number of painful procedures over longer hospitalizations, are less physiologically stable, and may have more fragile skin integrity than older preterm infants. Thus, the objective of the present study was to conduct a meta-analysis and narrative synthesis to examine the effectiveness of skin-to-skin contact for pain in younger preterm infants. Four pain-related distress outcomes (Premature Infant Pain Profile/Premature Infant Pain Profile-Revised [PIPP/PIPP-R], cry duration, heart rate, oxygen saturation), across four time points surrounding an acutely painful procedure (pre-procedure [baseline], during procedure, within 2-minutes post-procedure, greater than 2-minutes post procedure) were examined. Twenty-four studies were included in our review. In our meta-analyses, SSCP showed mixed evidence of significantly reduced pain-related outcomes, but the magnitude of the effects varied significantly according to outcome and time point. Our narrative syntheses examined heterogeneous, 'non-standard care' comparisons. Results suggest SSCP may not provide better pain management than sweet-tasting solutions. Overall, the certainty of the evidence base, using GRADE criteria, ranged from very low to low. Certainty was downgraded due to small numbers of studies, heterogeneity among studies, and poor reporting. These findings call for better quality trials. This extremely vulnerable group deserves special attention as the evidence is unclear about the benefits of SSCP, a critical pain management intervention for infants of a higher gestational age. REGISTRATION: INPLASY protocol 202470099 (doi:10.37766/inplasy2024.7.0099). PERSPECTIVE: This systematic review and meta-analysis examined the effectiveness of skin-to-skin contact for pain in younger preterm infants across four time points and four outcomes. The certainty of our findings was downgraded due to small numbers of studies, heterogeneity in study methodology, and biased methodologies, calling for better quality trials.
Electrochemical synthesis provides a promising strategy in the synthetic industry because of its benign conditions, strong economic viability, and environmental friendliness, but its application in the synthesis of COFs is still challenging. Here, we report an electrochemical-assisted synthesis strategy to prepare imine-linked COFs directly from inexpensive aromatic multialcohols via in situ formation of aldehyde monomers followed by a Schiff base reaction with amine monomers in one pot. Unlike conventional strategies, this synthetic methodology avoids the time-consuming presynthesis and purification steps of organic monomers, enabling the economical and efficient fabrication of imine-linked COFs. Three aromatic multialdehydes and 11 different COFs are successfully synthesized, and compared with COFs made via other reported procedures, the obtained COFs have higher crystallinity and porosity. Furthermore, highly efficient electrochemical oxidation of multialcohols into multialdehydes using KBr/ABNO as a double mediator was first demonstrated, resulting in the distillation-free synthesis of high-purity aldehydes (>98% purity) by simple filtration, which deserves broader investigation for other porous organic materials.
Ichnofossils are sedimentological structures left by humans and other organisms in the environment of the past. They can represent different activities of organisms but rarely can provide information about their behaviour. From this point of view, the "Devil's trails" fossil footprints are exceptionally important since they show some of the oldest human footprints and trails in Europe and give a glimpse into the locomotor control ability of Middle Pleistocene humans. Impressed on a volcanic rock in a remote locality of Southern Italy, their extreme scientific importance deserves to be shared with the scientific community for further studies and novel interpretations. By using complex photogrammetric methods, we digitised the entire area bearing the imprints and shared the 3D model to provide a digital heritage of the site. In addition, by means of virtual reality technologies, we provided a virtual experience for an inclusive dissemination of this unique palaeontological site.
Gut microbiota can modulate the tumor microenvironment and influence therapeutic outcomes in breast cancer. We hypothesized that similar interactions occur between the breast microbiota and tumor microenvironment. This exploratory study evaluated whether in situ microbial and macrophage densities differ between good and poor neoadjuvant chemotherapy responders and compared microbial density and composition post treatment with surgery-only controls. In 20 postmenopausal estrogen receptor-positive breast cancer patients, bacterial density was quantified by fluorescence in situ hybridization and macrophages density by multiplexed immunofluorescence in pre and post treatment tissue. Bacterial composition was analyzed by 16S rRNA sequencing of post-treatment resection specimens. Nine surgery-only patients served as controls. Neoadjuvant chemotherapy significantly reduced CD68 macrophage density, but not CD163 macrophages or bacterial density. Macrophages and bacterial densities were not correlated, and bacterial densities did not differ between good and poor responders. Higher pretreatment CD68 and CD163 macrophage densities predicted good response. Post treatment resections showed reduced bacterial density and alpha-diversity compared to surgery-only controls. These findings suggest that neoadjuvant chemotherapy affects local breast microbiota and macrophages, with macrophages as promising biomarkers to predict treatment response. The interaction between breast microbiota and local immunity deserves more attention in future research.
Hepatic encephalopathy is secondary to liver failure and is prevalent in 20%-40% of cirrhosis patients. The cause involves ammonia toxicity, gut-brain interactions, and inflammation usually involving the microbiome. The aim was to review succinct management of microbiome disturbances. The purpose includes an argument for further research into the possible selective benefit of lactose and dairy products in managing chronic hepatic encephalopathy in lactose maldigesters. Articles from 1970 to June 2025 were sought on PubMed and Google Scholar, as well as individual articles, regarding using altered microbiome and hepatic encephalopathy management. Non-digestible disaccharides and synthetic polymers, often combined with non-absorbable antibiotic rifaximin, have been found to benefit hepatic encephalopathy. It is of note that after a few reports, lactose was abandoned as a potential treatment in lactase non-persistent cirrhotic patients. After abandonment for unclear reasons, colonic adaptation in lactase non-persistent populations was clearly defined to be associated with microbiome changes similar to other non-absorbable disaccharides. While current treatment is acceptable to most patients, the potential role of lactose and dairy products likely deserves further studies in patients with lactase non-persistence. The process of colonic adaptation may favour improvement in hepatic encephalopathy by altering the bacterial milieu. Use of dairy foods could also improve nutrition in cirrhosis. As such, use of lactose or dairy products could have a wide application since cirrhosis is common in parts of the world where lactose maldigestion is also widespread. Confusion related to advanced liver disease is thought to be related to failure to detoxify urea from protein by the liver. Contributing to ammonia production are bacteria in the lower intestine, and part of the treatment is to change the microenvironment and reduce ammonia production. This article reviews agents that can do this. Standard accepted treatments include certain sugars, such as lactulose. Other ways are to treat with an antibiotic that does not get into the body's circulation and a cleansing powder used to prepare for colonoscopy. A more radical way is to use fecal transplantation from a healthy person. A major focus of this article is to re-establish a rationale for studying the possible benefits of the milk sugar lactose in those who, as adults, do not digest it due to a genetic loss of the intestinal enzyme. It has been observed that consuming regular quantities of lactose (milk and dairy products) leads to expansion of bacteria that do not produce ammonia and mimic effects of lactulose. Prior to these observations, several reports supported the potential benefit of using lactose for patients with advanced liver disease. However, all research on this ended. The reason for this was unclear. The question of why lactose was abandoned was posed to an artificial intelligence chatbot, which answered that the response was erratic and no better than lactulose. This answer did not take into consideration later findings. Since the adult inability to digest lactose affects about two thirds of the world's population, and liver disease is quite common in geographic areas of the world with predominance of this genetic trait, it would be reasonable to carry out further trials with this potential natural milk sugar on such patients with advanced liver diseases.
The significant impact of attention deficit/hyperactivity disorder (ADHD) on health in adult life has been widely recognized. Among the comorbidities of this disorder in later life, dementia is one of the most relevant ones. We performed a systematic review and meta-analysis to explore the impact of previous ADHD diagnosis on dementia risk. We systematically searched Pubmed, Embase and Scopus for the relevant literature. Cohort and case-control studies were included in our review. Retrieved records were selected by title and abstract and then by full text reading. For quality appraisal, the Newcastle-Ottawa scale was used. A meta-analysis of hazard ratios (HRs) was performed for each type of dementia. Four cohort studies and one case-control study were included, for a total of 3,703,877 and 400 participants, respectively. For all-cause dementia, the pooled HR was 2.52 (95%CI 1.51-4.22, p < 0.001), pointing out a significantly higher hazard in subjects with ADHD. For Alzheimer's disease, vascular dementia and Lewy body dementia, no meta-analysis was performed due to the low number of available studies. Our results support a significant association between ADHD and risk of dementia. The results regarding specific types of dementia are more challenging to interpret and could have been influenced by sample size issues. These findings show that ADHD deserves attention in future research on cognitive disorders of the elderly; in particular, more studies are needed to reveal if a true causal relationship links ADHD and dementia.
The Qinghai-Xizang Plateau has a unique environment with high biodiversity and serves as a key eco-security shield in Asia, yet fungal diversity in Xizang remains poorly studied. In this study, we describe a new species of Kuehneromyces sejilaensis collected from Xizang. The species is characterized by a pileus with a white center and striate margin; broadly ellipsoid and small basidiospores with a germ pore that are dextrinoid in Melzer's reagent, and utriform pleurocystidia with a long-attenuated apex. Phylogenetic analyses based on combined ITS, LSU, rpb2, and tef1-α sequences supports Kuehneromyces sejilaensis forms a distinct branch within the genus. This study enriches the diversity of the genus and highlighting its unique geographical distribution and suggests that fungal diversity in the Xizang region deserves further attention and research.
Women in medicine often delay childbearing due to the competing priorities of training, finding a partner, and waiting for the "right time." Unfortunately, the steep decline in female fertility during a woman's mid to late 30s also often coincides with the completion of residency and/or fellowship training. Data show that women in medicine elect to have children later in life and that at least 1 in 4 female physicians suffer from infertility, a higher rate than in nonphysicians. It is essential to escalate the dialogue regarding family planning for female physicians and trainees. In this review, we discuss markers currently used to evaluate ovarian reserve, including anti-Müllerian hormone. We also discuss common methods for fertility preservation, including egg/oocyte and embryo cryopreservation, and unique logistical challenges this population faces in family planning. Narrative review of literature regarding fertility, markers of ovarian reserve, fertility preservation options, and family-planning challenges, particularly pertaining to the population of women in medicine. Women in medicine experience higher rates of infertility compared with the general population and frequently delay childbearing due to training and career demands. This is a narrative review and is limited by the available published literature, including a relative paucity of data surrounding fertility and fertility preservation outcomes among female physicians and trainees. Women in medicine must be viewed as a critical at-risk population for infertility with unique and multifactorial family-building challenges. This underrecognized group deserves heightened attention, with a special emphasis on the key elements of education, mentorship, and support.
To assess the efficacy and safety of intravenous remimazolam besylate for sedation during dental procedures in patients with cognitive disabilities, a group frequently managed under general anesthesia due to poor cooperation and increased perioperative risks. In this single-center prospective single-arm observational study, 43 adult patients with cognitive or motor disabilities (ASA II-III) received outpatient dental care under intravenous remimazolam. Sedation was titrated to moderate levels according to EMA and IACSD guidelines. Outcomes included procedural success, Ramsay Sedation Scale, Post-Anesthetic Discharge Scoring System (PADSS), Modified Aldrete Score (MAS), vital signs, drug dosage, recovery, adverse events, and caregiver feedback. All treatments were successfully completed without anesthesiologist intervention or flumazenil reversal. Mean onset of sedation was 3.8 ± 2.3 min, recovery time 47 ± 20.4 min, and time to discharge 72.5 ± 22.5 min. The mean total remimazolam dose was 14 ± 5.9 mg. Most patients reached Ramsay 4, while 9.7% remained ≤ 3. Vital parameters remained stable with no episodes of hypoxemia or airway compromise. At discharge, PADSS averaged 8.9 ± 1.0 and MAS 9.4 ± 0.6, confirming recovery despite motor or neurological limitations affecting PADSS scoring. Caregiver interviews indicated that 42% of patients slept during the day, 85% slept normally at night, 68% appeared calmer, and only 7% experienced minor adverse effects such as nausea or brief agitation. Remimazolam provided safe and effective intravenous sedation with rapid onset and reliable recovery. Combining PADSS with MAS improved discharge assessment in this patient population. Remimazolam deserves further investigation as a potential practical alternative to general anesthesia for dental procedures in patients with cognitive disabilities, with the potential to enable safe care, procedural success, and favorable recovery profiles. International Standard Randomised Controlled Trial Number (ISRCTN) registry, ISRCTN39322806. Retrospectively registered on 10 November 2025.
Neoadjuvant treatment for locally advanced rectal cancer (LARC) evolves rapidly, and targeted agents could play a relevant role. In the phase II RAX study, we investigated the efficacy and safety of neoadjuvant chemoradiotherapy (CRT, 25 × 2 Gy with twice daily 825 mg/m2 capecitabine) combined with bevacizumab (5 mg/kg, day: 14, 1, 15, 29 of CRT) followed by surgery. Patients with cT4 tumors, cT3 within 5 cm from the anal verge, or high cT3 within 2 mm of the mesorectal fascia (MRF) were included. Safety was presented in terms of number of toxicity failures, according to protocolized criteria based on expected toxicity of CRT and bevacizumab, and severe adverse events. Histopathological response was described in terms of extent (according to Mandard's Tumor Regression Grade) and pattern (shrinkage vs. fragmentation). Efficacy outcomes were histopathological response, incidence of locoregional recurrences (LRR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). We included 35 patients; 66% were male with a median age of 61 years (range, 25-77). About 71% of tumors involved the MRF at baseline, 56% were cT4, and 71% were cN+. Eight patients developed toxicity failures (3 bowel perforations, 2 pulmonary embolisms, 2 bleedings, and 1 anal mucositis requiring surgery). These toxicity failures exceeded the predefined stopping rules and led to study termination after 35 patients. Pathological complete response was observed in 4 patients, and 1 was ypT0N1 (total 15%), and 5 more achieved a major response (TRG1). Ten-year incidences of LRR and DM were 6% (95% confidence interval [CI], 0%-13%) and 31% (95% CI, 16%-47%), respectively; both DFS and OS were 60% (95% CI, 44%-76%). Neoadjuvant CRT with concomitant bevacizumab results in high DFS and OS after long follow-up, but with concerning numbers of early toxicity failures. Incorporating bevacizumab into neoadjuvant treatment of LARC, possibly in combination with novel therapeutic strategies, may result in promising long-term oncological outcomes and deserves further investigation.
Language plays a central role in shaping healthcare culture, relationships, and expectations. Within alcohol and other drug (AOD) treatment, the term patient remains widely used, including within patient-reported outcome and experience measures (PROMs and PREMs). Yet in a treatment context that increasingly emphasizes collaboration, autonomy, and recovery-oriented care, the continued use of the patient deserves closer scrutiny. This commentary argues that the patient is not a neutral descriptor in AOD settings. The term may shape how people experience services, how they understand their role in treatment, and their willingness to engage with care. Where it is experienced as passive, hierarchical, or inconsistent with the relational and collaborative nature of AOD treatment, it may undermine engagement and potentially influence outcomes. Terminology may also influence how clinicians perceive and interact with the people they support. These concerns are especially relevant in PROMs and PREMs, where patient-based language sits uneasily alongside the person-centered values these measures are intended to reflect and promote. Reframing these tools as person-reported outcome and experience measures would represent a simple and practical step toward greater alignment. This commentary was further informed through consultation with a Consumer Advisory Group, whose lived and living experience perspectives highlighted the importance of language that conveys dignity, agency, and respect within treatment settings. Their input reinforced the need for terminology that reflects collaborative and recovery-oriented models of care. Although current evidence is insufficient to justify a single universally preferred alternative, and further research is needed to better understand how terminology influences engagement and experiences of care, more person-centered language practices are both possible and necessary. These include referring to individuals by name and directly asking how they wish to be addressed. Greater attention to language offers a practical opportunity to better align AOD services with the collaborative and recovery-oriented values they increasingly seek to embody.
Hypopharyngeal squamous cell carcinoma (HSCC) is often diagnosed at an advanced stage and characterized by poor prognosis. While primary (chemo)radiotherapy is frequently preferred for early and intermediate stage disease, total laryngopharyngectomy (TLP) remains the gold standard for the primary treatment of locally advanced tumors and for salvage treatment of residual and recurrent HSCC. However, reconstruction of a circumferential hypopharyngeal defect is challenging. This retrospective cohort analysis evaluates the oncological and functional outcomes of TLP with free jejunal transfer (FJT). 22 patients with histopathologically confirmed HSCC requiring TLP with FJT were included. Data on patient demographics, tumor characteristics, and functional and oncological outcomes were analyzed with overall survival (OS) as primary outcome. Overall, 22 patients were included (18.2% female, mean age 65.6 years). Mean follow-up time was 3.9 years. Primary and salvage TLP was performed in 8 (36.4%) and 14 (63.6%) patients respectively. All primary tumors were stage IV. In the salvage group, patients had disease stage II (n = 1, 7.1%), III (n = 5, 35.7%) and IV (n = 8, 57.1%). Successful FJT was achieved in 95.5% of patients with only 1 FJT failure (4.5%). Pharyngocutaneous fistula (PCF) formation was the most common complication and was observed in 6 patients (27.3%); 2 were managed conservatively and 4 required surgical intervention. No in-hospital deaths were encountered. Two- and five-year OS rates were 52.3% and 26.9%, respectively. Disease-specific survival (DSS) rates were 54.7% and 42.8% respectively. Complete oral intake and voice rehabilitation were achieved in 68.2% and 52.3% of patients respectively. FJT deserves its place in the reconstructive armamentarium following TLP. Oncological outcomes are good and functional outcomes are acceptable but there is room for improvement.
Invasive cervical cancer is a very common cause of cancer death in women worldwide, primarily due to late detection of this cancer. The clinical manifestations of cervical cancer vary significantly and are difficult to predict. Finding new effective biomarkers for the early detection of cervical cancer is essential to reducing mortality. Small microRNA molecules have also recently emerged as potential biomarker candidates in the diagnosis of cervical cancer. Despite analytical limitations in microRNA assays and the lack of automated and standardized tests, validated and prospective systematic evaluation of this new parameter in cervical cancer deserves further development. This review describes the importance and potential usefulness of microRNAs in detecting cervical cancer at an early stage, monitoring the course of the disease, and assessing the effectiveness of treatment. The diagnostic importance of microRNAs is well documented in many publications, suggesting that, as microRNA research progresses, they may become a useful diagnostic tool for cervical cancer.
To determine whether a structured early nephrology consultation triggered by a machine-learning acute kidney injury (AKI) risk score (electronic signal to prevent AKI [ESTOP-AKI]) in patients at high risk for stage 2 AKI improves patient outcomes. This randomized clinical trial was conducted at the University of Chicago, Illinois, from March 13, 2019, to August 21, 2024, in hospitalized patients with no serum creatinine (SCr)-based AKI and an ESTOP-AKI score more than 0.01. Patients were randomized to receive a structured early nephrology consultation (ENC) from an attending nephrologist or usual care (UC). The ENC included an in-person assessment and recommendations regarding volume status, kidney perfusion, medication dosing and selection, electrolytes, nutritional needs, and further testing. Patients in the UC arm only received a nephrology consultation when clinically requested by the primary team. The primary outcome was the peak change in SCr from enrollment (ΔSCr) during the 7-day follow-up. Secondary outcomes included development of AKI, need for kidney replacement therapy, and inpatient and 90-day mortality. Of the 180 patients randomized (median [IQR] age, 62.5 [50.0-71.0] years; 102 males [56.7%]), 89 (49.4%) received ENC, and 91 (50.6%) received UC. There was no significant adjusted mean (SE) difference in the 7-day ΔSCr between the ENC and UC groups, adjusted for the ESTOP risk group (0.04 [0.07] mg/dL vs -0.03 [0.07] mg/dL; P = .30), among the 70 patients (38.9%) in the development of stage 1 or higher AKI (37 [42%] vs 33 [36%]; P = .47) or among the 29 patients (16.1%) with stage 2 or higher AKI (17 [19%] vs 12 [13%]; P = .28). During the study period, there were 121 ENC consultations containing 270 recommendations compared with 19 UC consultations and 36 recommendations. Medication dosage and discontinuation, diuretics or fluids, and vasopressor recommendations were more likely to be completely followed in the UC arm (15 of 22 [68%]) compared with in the ENC arm (48 of 116 [41%]). Over the 90-day follow-up, there was no significant difference in readmission rates (ENC: 30 [34.1%] vs UC: 40 [44.4%]; P = .21) or 90-day mortality (ENC: 13 [14.8%] vs UC: 17 [18.7%]; P = .62) between the ENC and UC arms. In this randomized clinical trial of structured ENC triggered by a machine-learning AKI risk score, there was no difference in ΔSCr. AKI consultation recommendations were not followed the majority of time; whether increasing adherence to recommendations could improve outcomes deserves further study. ClinicalTrials.gov Identifier: NCT03590028.
Among F8 mutation types, main determinants of inhibitor development after replacement therapy in Hemophilia A (HA), nonsense mutations display wide variation in the associated risk. Translational readthrough (Rdthr) at premature termination codons (PTCs) produces traces of full-length factor VIII (FVIII) including missense and wild-type molecules (WT Rdthr), and may influence the immune response involved in inhibitor formation. For inhibitor association analysis, we investigated F8 genotypes, inhibitor status and Rdthr features in 335 PTCs (1048 patients), recorded in the European Association for Haemophilia and Allied Disorders (EAHAD) database, and exploited expression of F8 PTCs variants. Mean-differences in affinity of HLA-DR alleles for FVIII WT peptides and their missense counterparts were bioinformatically calculated. WT Rdthr was higher for patients affected by PTCs not associated with inhibitor and was not predicted at all in patients with PTCs detected in at least three inhibitor positive cases (n = 136, p = 0.0001). WT Rdthr was lower for PTCs in the inhibitor prone FVIII light chain. Among FVIII PTCs fused with luciferase, quantitative output of WT Rdthr negative and positive groups did not differ, potentially highlighting for the positive group the importance of WT Rdthr to decrease inhibitor association. Readthrough output was the lowest among WT Rdthr negative PTCs, highly associated with inhibitors. The WT Rdthr prediction was extended to all PTCs that could arise by single nucleotide variations for the entire F8 coding sequence. Estimated WT Rdthr was higher in PTCs reported in EAHAD than those predicted (n = 662), foreseeing a higher risk of developing inhibitors. In silico mean differences in affinity of HLA-DR alleles for WT FVIII peptides and their missense counterparts, potentially arising from Rdthr of PTCs without WT formation (n = 297), were higher for missense variants predicted in patients with inhibitors than without (p < 0.0001), and increased for PTCs present in more than one patient with inhibitor, potentially supporting immunogenic features. The new genetic classification of HA PTCs may improve our knowledge about their relationship with inhibitors. It deserves to be explored for estimating inhibitor PTC association in HLA genotyped patients as well as in other human diseases.
Heavy metal and plastic pollution are one of most serious environmental problems, which threaten ecological environment and human health. Herein, plastics could be aged fragmented to nanoplastics (NPs) and Cadmium (Cd) as one of the most prevalent heavy metals was found in polluted soil in China. Additionally, Cd and NPs are widespread coexistence in aquatic and mammals. Additionally, the rate of premature births and the death of infants is increasing, and environmental pollution is one of main factors. Therefore, the impact of environmental pollution on pregnant women deserves more attention. In this study, the pregnant C57BL/6 J mice were exposed to PS-NPs and/or Cd from gestational day 0.5 to 15.5, and we explored the impact and potential mechanism of maternal co-exposure to PS-NPs and Cd on placenta-uterus micro-environment in mice and using inhibitors for verification. The results indicated that co-exposure PS-NPs and Cd caused more serious impairment in gut, placenta and uterus barrier, promoted more Cd accumulation, and affected the metal transporters and the homeostasis of glycolipid metabolism, thereby inducing mtROS mediated excessive mitophagy, causing the impairment of uterus and placenta structure and function. Additionally, mtROS and VDAC1 plays a vital role in this process via inhibitors intervention. Generally, we have proven that PS-NPs can adsorb Cd, impair the uterine-placental barrier, thereby promoting the accumulation of Cd and mtROS mediated VDAC1-mitophagy is the key signal pathway for the adverse effects caused by Cd and PS-NPs co-exposure during pregnancy.