Genetic Prediction of Osteoporosis by Anti-Müllerian Hormone Levels and Reproductive Factors in Women: A Mendelian Randomization Study.

Previous observational studies have suggested that anti-Müllerian hormone (AMH) and reproductive factors are linked to reduced bone mineral density (BMD) and an increased risk of osteoporosis (OP) in women. However, related studies are limited, and these traditional observational studies may be subject to residual confounders and reverse causation, while also lacking a more comprehensive observation of various reproductive factors. Univariate and multivariate two-sample Mendelian randomization analyses were conducted to determine the causal associations of AMH levels and six reproductive factors with BMD and OP, using the random-effects inverse-variance weighted method. Heterogeneity was assessed using Cochran's Q-statistic, and sensitivity analyses were performed to identify causal correlations. Age at menarche (AAM) was negatively associated with total body BMD (TB-BMD) in females aged 45-60 and over 60 years, as well as with heel bone mineral density (eBMD). Conversely, age at natural menopause (ANM) was positively associated with TB-BMD in the same age ranges and with eBMD. ANM was only causally associated with self-reported OP and showed no significant correlation with definitively diagnosed OP. Neither AMH level nor other reproductive factors were significantly associated with a genetic predisposition to BMD at any age and OP. Later AAM and earlier ANM are significantly genetically causally associated with decreased BMD but not with OP. AMH levels, length of menstrual cycle, age at first birth, age at last birth, and number of live births, in terms of genetic backgrounds, are not causally related to BMD or OP.

Safety evaluation and effects of dietary phlorotannins on the growth, health, and intestinal microbiota of Litopenaeus vannamei.

Phlorotannins are phenolic compounds with diverse biological activities, yet their efficacy in aquatic animals currently remains unclear. This investigation scrutinized the influence of phlorotannins on the growth, immunity, antioxidant capacity, and intestinal microbiota in Litopenaeus vannamei, concurrently evaluating the potential adverse effects of phlorotannins on L. vannamei. A base diet without phlorotannins supplementation was used as a control, and 4 groups of diets with different concentrations (0, 0.5, 1.0, 2.0 g kg-1) of phlorotannins were formulated and fed to juvenile shrimp (0.25 ± 0.01 g) for 60 days followed by a 24-hour challenge with Vibrio parahaemolyticus with triplicate in each group. Compared with the control, dietary 2.0 g kg-1 phlorotannins significantly improved the growth of the shrimp. The activities of enzymes related to cellular immunity, humoral immunity, and antioxidants, along with a notable upregulation in the expression of related genes, significantly increased. After V. parahaemolyticus challenge, the cumulative survival rates of the shrimp demonstrated a positive correlation with elevated concentrations of phlorotannins. In addition, the abundance of Bacteroidetes and functional genes associated with metabolism increased in phlorotannins supplementation groups. Phlorotannins did not elicit any detrimental effects on the biological macromolecules or histological integrity of the hepatopancreas or intestines. Simultaneously, it led to a significant reduction in malondialdehyde content. All results indicated that phlorotannins at concentrations of 2.0 g kg-1 can be used as safe feed additives to promote the growth, stimulate the immune response, improve the antioxidant capacity and intestinal health of L. vannamei, and an protect shrimp from damage caused by oxidative stress.

A Delphi Method Comfort Status Scale for Patients With Lung Cancer After Thoracoscopic Surgery.

PURPOSE: To construct the comfort status scale for patients with lung cancer after thoracoscopic surgery. DESIGN: Delphi method inquiry to 15 clinical and nursing experts. METHODS: On the basis of the comfort status scale and the subjective experience and objective symptoms of patients with lung cancer after thoracoscopic surgery, the relevant literature was consulted, semistructured interviews and group discussions were conducted, the pool of items of the postoperative comfort status scale for patients with lung cancer was initially formed, and the postoperative comfort status scale for patients with lung cancer was finally established. FINDINGS: The positive coefficient of experts was 100%, the coefficient of authority was 0.92 and 0.93, and the Kendal's W was 0.257 and 0.298, the degree of coordination of expert opinions was statistically significant (P < .05). Finally, a total of 28 items in four dimensions were formed to assess the postoperative comfort status of patients with lung cancer after thoracoscopic surgery. CONCLUSIONS: The Delphi method-based comfort status scale for patients with lung cancer after thoracoscopic surgery is scientific and reliable, and can provide a quantitative basis for the evaluation of the comfort status of patients after lung cancer thoracoscopic surgery, to further provide individual comfort care measures.

Nitrogen-Rich Triazine-Based Covalent Organic Frameworks as Efficient Visible Light Photocatalysts for Hydrogen Peroxide Production.

Covalent organic frameworks (COFs) have been widely used in photocatalytic hydrogen peroxide (H2O2) production due to their favorable band structure and excellent light absorption. Due to the rapid recombination rate of charge carriers, however, their applications are mainly restricted. This study presents the design and development of two highly conjugated triazine-based COFs (TBP-COF and TTP-COF) and evaluates their photocatalytic H2O2 production performance. The nitrogen-rich structures and high degrees of conjugation of TBP-COF and TTP-COF facilitate improved light absorption, promote O2 adsorption, enhance their redox power, and enable the efficient separation and transfer of photogenerated charge carriers. There is thus an increase in the photocatalytic activity for the production of H2O2. When exposed to 10 W LED visible light irradiation at a wavelength of 420 nm, the pyridine-based TTP-COF produced 4244 µmol h-1 g-1 of H2O2 from pure water in the absence of a sacrificial agent. Compared to TBP-COF (1882 µmol h-1 g-1), which has a similar structure but lacks pyridine sites, TTP-COF demonstrated nearly 2.5 times greater efficiency. Furthermore, it exhibited superior performance compared to most previously published nonmetal COF-based photocatalysts.

Neighborhood Racial and Ethnic Segregation and the Risk of Dementia in Older Adults Living with Kidney Failure.

BACKGROUND: Dementia disproportionately impacts older minoritized adults with kidney failure. To better understand the mechanism of this disparity, we studied the role of racial and ethnic segregation (segregation hereafter), a form of structural racism recently identified as a mechanism in numerous other health disparities. METHODS: We identified 901,065 older adults (age ≥55) with kidney failure from 2003 to 2019 using the United States Renal Data System (USRDS). We quantified dementia risk across tertiles of residential neighborhood segregation score using cause-specific hazard models, adjusting for individual and neighborhood-level factors. We included an interaction term to quantify the differential effect of segregation on dementia diagnosis by race and ethnicity. RESULTS: We identified 79,851 older adults with kidney failure diagnosed with dementia between 2003 and 2019 (median follow-up: 2.2 years). Compared to those in low-segregation neighborhoods, older adults with kidney failure in high-segregation neighborhoods had a 1.63-fold (95% confidence interval (CI):1.60-1.66) higher risk of dementia diagnosis, an association that differed by race and ethnicity (Asian: adjusted hazard ratio [aHR]=1.26, 95%CI:1.15-1.38; Black: aHR=1.66, 95%CI:1.61-1.71; Hispanic: aHR=2.05, 95%CI:1.93-2.18; White: aHR=1.59, 95%CI:1.55-1.64;Pinteraction<0.001). Notably, older Asian (aHR=1.76, 95%CI:1.64-1.89), Black (aHR=2.65, 95%CI:2.54-2.77), Hispanic (aHR=2.15, 95%CI:2.04-2.26), and White (aHR=2.20, 95%CI:2.09-2.31) adults with kidney failure residing in minority-predominant high-segregation neighborhoods had a higher risk of dementia diagnosis compared to older White adults with kidney failure in White-predominant high-segregation neighborhoods. Moreover, older adults with kidney failure receiving care at dialysis facilities located in high-segregation neighborhoods also experienced a higher risk of dementia diagnosis (aHR=1.53, 95%CI:1.50-1.56); this association differed by race and ethnicity (Pinteraction<0.001). CONCLUSIONS: Residing in or receiving care at dialysis facilities located in high-segregation neighborhoods was associated with a higher risk of dementia diagnosis among older individuals with kidney failure, particularly minoritized individuals.

Posterior mediastinal leiomyosarcoma: Case report and literature review.

BACKGROUND: Posterior mediastinal leiomyosarcoma is an extremely rare malignant mesenchymal tumor with no special clinical symptoms, which is easily confused with some common tumors in the posterior mediastinum, affecting the accuracy of the first diagnosis by clinicians and delaying the treatment of patients. CASE SUMMARY: We report a 59-year-old woman with a space-occupying lesion in the posterior mediastinum. The patient was mistakenly diagnosed with lumbar muscle or vertebral body lesions due to chest and back pain and underwent conservative treatment, but her symptoms did not improve significantly and she gradually developed pain in both lower limbs. Chest computed tomography (CT) scan indicated the left lower lung paraspinal space and underwent standard single-aperture video-assisted thoracoscopic surgery (VATS), which was pathologically confirmed as posterior mediastinal leiomyosarcoma. CONCLUSION: Complete surgical resection of posterior mediastinal leiomyosarcoma can achieve good clinical results.

Organic Pollutant Exposure and CKD: A Chronic Renal Insufficiency Cohort Pilot Study.

Rationale & Objective: This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD). Study Design: This was a cross-sectional and longitudinal analysis. Setting and Participants: Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Exposures: Exposure at baseline and longitudinally to various organic chemical pollutants. Outcomes: The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR. Analytical Approach: We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants. Results: Median baseline eGFR and urinary protein-to-creatinine ratio were 33 mL/min/1.73 m2 and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes. Limitations: Small sample size, evaluation of single rather than combined exposures. Conclusions: Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function.

The effect of exposure to organic pollutants has not been studied in adults with chronic kidney disease. (CKD). To fill this gap, we measured the exposure to a wide range of chemicals that are found in plastics, personal care products, and food preparation. Overall, the exposure was similar to that noted in the healthy population living in the United States. Only select compounds, mainly phthalates, demonstrated a trend with a more rapid decline in kidney function. These findings provide a useful reference for future studies that aim to evaluate organic pollutant exposure in patients with CKD. This is significant because these exposures represent a modifiable risk factor for disease progression through alterations in diet or lifestyle.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Multifunctional agents based on 3-dicycanovinylindan-1-one acceptor: Molecular design and phototheranostic application.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered considerable attention in recent years, owing to its precise spatiotemporal accuracy with minimal side effects. Recent research reveals that the combination of PDT and PTT exhibits a remarkable anti-tumor efficacy compared to PDT or PTT alone, which has put forward the new requirements of multifunctional phototherapy agents with both high photosensitization and photothermal conversion efficiencies. Among the newly developed multifunctional agents, the ones with one or two 3-dicycanovinylindan-1-one (IC) moieties as the acceptors attract much more attention, due to their long-wavelength excitation and emission, as well as high phototherapy efficacies. Therefore, in this review, the latest advancement of multifunctional agents based on IC acceptor is summarized. Especially, we focus on the structure-property relationships of the agents, as well as their biomedical application in anti-tumor therapy or image-guided therapy. Our perspective on the further future development of this field is also discussed to conclude.

Bayesian Averaging Evaluation Method of Accelerated Degradation Testing Considering Model Uncertainty Based on Relative Entropy.

To evaluate the lifetime and reliability of long-life, high-reliability products under limited resources, accelerated degradation testing (ADT) technology has been widely applied. Furthermore, the Bayesian evaluation method for ADT can comprehensively utilize historical information and overcome the limitations caused by small sample sizes, garnering significant attention from scholars. However, the traditional ADT Bayesian evaluation method has inherent shortcomings and limitations. Due to the constraints of small samples and an incomplete understanding of degradation mechanisms or accelerated mechanisms, the selected evaluation model may be inaccurate, leading to potentially inaccurate evaluation results. Therefore, describing and quantifying the impact of model uncertainty on evaluation results is a challenging issue that urgently needs resolution in the theoretical research of ADT Bayesian methods. This article addresses the issue of model uncertainty in the ADT Bayesian evaluation process. It analyzes the modeling process of ADT Bayesian and proposes a new model averaging evaluation method for ADT Bayesian based on relative entropy, which, to a certain extent, can resolve the issue of evaluation inaccuracy caused by model selection uncertainty. This study holds certain theoretical and engineering application value for conducting ADT Bayesian evaluation under model uncertainty.

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study.

Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28-1.59; P = 6.66 × 10-11), ovarian cysts (OR = 1.36, 95% CI 1.20-1.55; P = 1.57 × 10-6), AUB (OR = 1.41, 95% CI 1.20-1.66; P = 3.01 × 10-5), and endometriosis (OR = 1.43, 95% CI 1.27-1.70; P = 2.21 × 10-7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

Neighborhood Segregation and Access to Live Donor Kidney Transplantation.

Importance: Identifying the mechanisms of structural racism, such as racial and ethnic segregation, is a crucial first step in addressing the persistent disparities in access to live donor kidney transplantation (LDKT). Objective: To assess whether segregation at the candidate's residential neighborhood and transplant center neighborhood is associated with access to LDKT. Design, Setting, and Participants: In this cohort study spanning January 1995 to December 2021, participants included non-Hispanic Black or White adult candidates for first-time LDKT reported in the US national transplant registry. The median (IQR) follow-up time for each participant was 1.9 (0.6-3.0) years. Main Outcome and Measures: Segregation, measured using the Theil H method to calculate segregation tertiles in zip code tabulation areas based on the American Community Survey 5-year estimates, reflects the heterogeneity in neighborhood racial and ethnic composition. To quantify the likelihood of LDKT by neighborhood segregation, cause-specific hazard models were adjusted for individual-level and neighborhood-level factors and included an interaction between segregation tertiles and race. Results: Among 162 587 candidates for kidney transplant, the mean (SD) age was 51.6 (13.2) years, 65 141 (40.1%) were female, 80 023 (49.2%) were Black, and 82 564 (50.8%) were White. Among Black candidates, living in a high-segregation neighborhood was associated with 10% (adjusted hazard ratio [AHR], 0.90 [95% CI, 0.84-0.97]) lower access to LDKT relative to residence in low-segregation neighborhoods; no such association was observed among White candidates (P for interaction = .01). Both Black candidates (AHR, 0.94 [95% CI, 0.89-1.00]) and White candidates (AHR, 0.92 [95% CI, 0.88-0.97]) listed at transplant centers in high-segregation neighborhoods had lower access to LDKT relative to their counterparts listed at centers in low-segregation neighborhoods (P for interaction = .64). Within high-segregation transplant center neighborhoods, candidates listed at predominantly minority neighborhoods had 17% lower access to LDKT relative to candidates listed at predominantly White neighborhoods (AHR, 0.83 [95% CI, 0.75-0.92]). Black candidates residing in or listed at transplant centers in predominantly minority neighborhoods had significantly lower likelihood of LDKT relative to White candidates residing in or listed at transplant centers located in predominantly White neighborhoods (65% and 64%, respectively). Conclusions: Segregated residential and transplant center neighborhoods likely serve as a mechanism of structural racism, contributing to persistent racial disparities in access to LDKT. To promote equitable access, studies should assess targeted interventions (eg, community outreach clinics) to improve support for potential candidates and donors and ultimately mitigate the effects of segregation.

A biodegradable semiconducting polymer phototherapeutic agent for safe cancer phototherapy.

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.

Reliability and validity analyses of the postoperative comfort scale for patients with lung cancer undergoing endoscopic surgery and an evaluation of patient comfort.

BACKGROUND: Lung cancer is one of the most common malignant tumours that threaten human health globally. Radical resection under thoracoscopic guidance has been accepted as the major therapeutic option for treating lung cancer clinically. However, the procedure still has some adverse impacts on the comfort of patients following thoracoscopic surgery. OBJECTIVE: To analyse the reliability and validity of the postoperative comfort scale for patients with lung cancer undergoing endoscopic surgery and to evaluate patient comfort. METHODS: With 210 patients with lung cancer undergoing endoscopic surgery as the participants, this study was performed to assess the reliability and validity of the postoperative comfort scale for patients with lung cancer undergoing endoscopic surgery, with the assessment performed by eight experts. RESULTS: The postoperative comfort scale included 28 items and consisted of four dimensions (physiological, psychological, socio-cultural and environmental). The total Cronbach's alpha coefficient of the scale was 0.851, and the split-half reliability coefficient was 0.875. Meanwhile, the content validity index (CVI) was 0.875∼1, and the scale-level average CVI was 0.99. The Chi-square/degree-of-freedom ratio of construct validity was 2.844, suggesting a good model-fitting. Furthermore, the overall average score of patient comfort was 3.72 ± 0.57, with scores ranging between 3.59 ± 0.71 and 3.83 ± 1.06 across all four dimensions, with the lowest score in the physiological dimension. CONCLUSION: The postoperative comfort scale has good reliability and validity and can be applied for the postoperative comfort assessment of patients undergoing endoscopic surgery for lung cancer. Overall, the degree of patient comfort in this assessment was moderate, meaning targeted measures may be required to further improve patient comfort, especially in the physiological dimension.

Dual/Multi-Modal Image-Guided Diagnosis and Therapy Based on Luminogens with Aggregation-Induced Emission.

The combination of multiple imaging methods has made an indelible contribution to the diagnosis, surgical navigation, treatment, and prognostic evaluation of various diseases. Due to the unique advantages of luminogens with aggregation-induced emission (AIE), their progress has been significant in the field of organic fluorescent contrast agents. Herein, this manuscript summarizes the recent advancements in AIE molecules as contrast agents for optical image-based dual/multi-modal imaging. We particularly focus on the exceptional properties of each material and the corresponding application in the diagnosis and treatment of diseases.

Regulation Strategy of Nanostructured Engineering on Indium-Based Materials for Electrocatalytic Conversion of CO2.

Electrochemical carbon dioxide reduction (CO2 RR), as an emerging technology, can combine with sustainable energies to convert CO2 into high value-added products, providing an effective pathway to realize carbon neutrality. However, the high activation energy of CO2 , low mass transfer, and competitive hydrogen evolution reaction (HER) leads to the unsatisfied catalytic activity. Recently, Indium (In)-based materials have attracted significant attention in CO2 RR and a series of regulation strategies of nanostructured engineering are exploited to rationally design various advanced In-based electrocatalysts, which forces the necessary of a comprehensive and fundamental summary, but there is still a scarcity. Herein, this review provides a systematic discussion of the nanostructure engineering of In-based materials for the efficient electrocatalytic conversion of CO2 to fuels. These efficient regulation strategies including morphology, size, composition, defects, surface modification, interfacial structure, alloying, and single-atom structure, are summarized for exploring the internal relationship between the CO2 RR performance and the physicochemical properties of In-based catalysts. The correlation of electronic structure and adsorption behavior of reaction intermediates are highlighted to gain in-depth understanding of catalytic reaction kinetics for CO2 RR. Moreover, the challenges and opportunities of In-based materials are proposed, which is expected to inspire the development of other effective catalysts for CO2 RR.

Novel MSH2 and TSC2 variants in a Chinese family with Lynch syndrome and their synergistic impact in urothelial carcinoma.

Lynch syndrome, an autosomal dominant hereditary disease arising from mutations in mismatch repair genes, is linked to the development of multiple tumor types, notably colorectal cancer, endometrial carcinoma and upper urinary tract urothelial carcinoma. In this study, we present the case of a young patient diagnosed with upper urinary tract urothelial carcinoma, notable for a familial history of diverse malignancies. By employing genetic analysis, we verified the presence of Lynch syndrome within the family and detected novel variants, MSH2 p.A604D and TSC2 p.C738Y, utilizing NGS technology. Subsequently, we conducted validation experiments to assess the pathogenicity of the MSH2 and TSC2 variants. We illustrated that the MSH2 variant can result in diminished MSH2 expression, compromised mismatch repair function, and induce resistance to cisplatin in urothelial carcinoma. Furthermore, we substantiated the promotional impact of the identified TSC2 variant on urothelial carcinoma, encompassing proliferation, invasion, and migration. Significantly, we found that the MSH2 p.A604D variant and TSC2 p.C738Y variant synergistically enhance the promotion of urothelial carcinoma.

Photoactuators Based on Plastically Flexible α-Cyanostilbene Molecular Crystals Driven by the Solid-State [2+2] Cycloaddition Reaction.

Organic photomechanical molecular crystals are promising candidates for photoactuators, which have potential applications as smart materials in various fields. However, it is still challenging to fabricate photomechanical molecular crystals with flexibility because most of the molecular crystals are brittle and the mechanism of flexible crystals remains controversial. Here, a plastically flexible α-cyanostilbene crystal has been synthesized that can undergo solid-state [2+2] cycloaddition reaction under violet or UV irradiation and exhibits excellent photomechanical bending properties. A hook-shaped crystal can lift 0.7 mg object upward by 1.5 cm, which proves its potential for application as photoactuators. When complex with the agarose polymer, the molecules will be in the form of macroscopic crystals, which can drive the composite films to exhibit excellent photomechanical bending performance. Upon irradiation with UV light, the composite film can quickly lift 18.0 mg object upward by 0.3 cm. The results of this work may facilitate the application of macroscale crystals as photoactuators.