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Yan-Qiu Liu,1 Yu-Lin Guo,2 Jia Xu,3 Wen-Jing Geng,1 Zhen-Zhen Li,4 Ming Jia,1 Yu-Dan Liu,1 Hua Zhao1 1College of Nursing, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of China; 2Department of Rehabilitation, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Nephrology, Shanxi Bethune Hospital, Taiyuan, Shanxi, People’s Republic of China; 4Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Hua Zhao, College of Nursing, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of China, Tel +86 13903465019, Email zhshun7788@126.comPurpose: To probe into the needs and barriers underlying patients’ participation in shared decision-making related to rehabilitation nursing for hemophilic arthropathy.Patients and Methods: The phenomenological research approach was adopted to conduct a series of semi-structured, in-depth interviews with 15 patients with hemophilic arthropathy undergoing rehabilitative treatments, 10 caregivers, and 7 healthcare providers from a hemophilia treatment center in Shanxi province, China. Colaizzi’s seven-step method of data analysis was applied to organize, analyze, and extract the themes from the interview materials.Results: Three main themes emerged from the analysis: the status quo of the healthcare system (insufficient decision support systems and mismatch between healthcare providers’ and patients’ resources), circumstances of provider–patient interactions (lack of information exchange and unbalanced power structure between healthcare providers and patients), and patient-related factors influencing participation in decision-making (lack of self-efficacy, personal characteristics, family and social decision support, and attitude toward participation in decision-making).Conclusion: Participation in rehabilitation decision-making among patients with hemophilic arthropathy is affected by multiple barriers. Healthcare professionals should improve their understanding of shared decision-making, offer patients active guidance on participating in the decision-making process, prioritize their affective needs, and formulate professional and effective solutions to support shared decision-making as early as possible.Keywords: hemophilic arthropathy, shared decision-making, rehabilitation program, nursing, joint function, qualitative research

Zhuo Wang,1,* Zun-Fu Ke,1,* Xiao-Fang Lu,1 Can-Jiao Luo,1 Yong-Dong Liu,1 Zhong-Wei Lin,2 Lian-Tang Wang1 1Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event. However, only a few of the causes of cases of HCC spontaneous regression are clear. More cases are ambiguous. We report on a patient who had a spontaneous regression of HCC as detected by histological and immunohistochemical exam, and compared this case to 20 cases of non-specific HCC. In our case, we found that the odd phenomenon is that CD163+ macrophages are overactivated in surviving HCC, which is spontaneously regressing. Concomitantly, we cannot find a similar phenomenon in peritumoral liver tissue or non-specific HCC. According to our microscopical morphology and immunohistochemical study, we considered that a clue of a possible etiology about HCC spontaneous regression is that CD163+ macrophages are overactivated. Keywords: hepatocellular carcinoma, spontaneous regression, macrophages, CD163, CD68

Polycrystalline Cu(InGaAl)Se 2 (CIGAS) thin films were prepared on polyimide (PI) foils by depositing aluminum (Al) and CIGS precursor layers. Three ceramic CIGS quaternary targets with different sodium (Na) contents were used for investigating the influences of alkali doping at an annealing temperature of 500 °C. The Al concentration was enriched at the front interfaces of absorber films with different Na doping amounts after annealing. Na in the precursor layer diffused to both interfaces during the annealing process, most Na diffused into the Mo layer, and Na existed in the annealed film as compounds Na 2 Se x and Na 2 SeO 3 . An appropriate amount Na element could be beneficial for grain growth in the region beneath the surface. Low Na doping had no significant effect on the crystallization property. High Na doping effected the diffusion of the Cu 2- x Se liquid phase and reduced the grain size. On the basis of good crystallization, the passivation effect of Na can effectively improve the performance of cells. A certified power conversion efficiency of 16.19% of a CIGAS flexible solar cell with a 0.54 cm 2 active area has been achieved.

Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P =0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P =0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3 , which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3 , P =0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3 , P =0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3 ]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P ＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P ＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞ 0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P ＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P ＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞ 0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P ＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P ＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞ 0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

Centella asiatica (L.) Urban is a medical plant rich in triterpenoids, frequently used in Asia to treat skin conditions such as acne. To search for anti-photoaging agents, 16 known triterpenoids and five undescribed triterpenoids, including three ursane, one oleanane and one nor-ursane were isolated from the whole herb of C. asiatica. The structures and relative stereochemistry of these compounds were elucidated by detailed NMR spectra and HRESIMS. Compounds 1 and 2 were isomers of ursane-type and oleane-type triterpenes with rare aldehyde groups on C-23. Compound 4 was a unique example of a nor-ursane type triterpenoid. The Ultraviolet B (UVB) induced HaCaT cell damage model was used to measure the in vitro anti-photoaging activity of all 21 compounds. Twenty compounds significantly increased HaCaT viability and inhibited lactate dehydrogenase (LDH) release after UVB exposure. These findings highlight the protective effects of C. asiatica-derived triterpenoids against UVB damage and indicate their potential as natural agents that can protect the skin against photoaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To identify toxicity drivers within poorly characterized high-molar-weight disinfection by-products (DBPs), relatively stable high-yield initial transformation products generated from aromatic amino acids and peptides and humic substances have drawn much attention. In this study, initial transformation products in chlorination of the indole moiety in tryptophan (Trp) are proposed and their formation mechanisms were investigated using a quantum chemical computational method. The results indicate that 3-Cl-Trp+ is initially formed after the Cl + of HOCl attacks the indole moiety, and nucleophilic addition with nucleophilic agents (H 2 O and OCl - ) is thermodynamically preferred over deprotonation to generate 2-X-3-Cl-indoline moiety (X = OH and OCl), which is in contrast to indole. Over 25 types of initial transformation products are proposed from the 2-X-3-Cl-indoline moiety and two ring opening pathways were found at N1-C2 and C2-C3 bonds. Significantly, most structures of initial transformation products proposed based on experimental detection m/z values were confirmed using quantum chemical calculations and some new products are proposed in this work. The results are helpful to expand our understanding of the intrinsic reactivity of aromatic ring towards chlorination by hypochlorous acid.

Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor obstetrical outcomes and a risk of recurrence as high as 100 %. This meta-analysis examined CIUE prevalence, recurrence, association with autoimmune disorders, reproductive outcomes, pregnancy complications, and the benefits of medical treatments. A systematic review, following PRISMA guidelines, involved a thorough search across multiple databases including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Evidence Based Medical Reviews, and Scopus. Out of 590 initially identified studies, 19 studies were included for both qualitative synthesis and meta-analysis after full-text review. Risk of bias was assessed using appropriate tools: The Risk Of Bias In Non-randomized Studies of Interventions tool was applied to twelve studies, while the Joanna Briggs Institute case series critical appraisal tool was used for seven studies. Our findings confirm that CIUE is a rare condition (0.7 %). CIUE is associated with decreased live birth rates (53 %), increased recurrent pregnancy loss (23 %), fetal loss beyond 22 weeks gestation (25 %), a higher prevalence of autoimmune diseases (14 %), and a recurrence rate of 30 % in subsequent pregnancies. Moreover, individuals with CIUE had higher rates of pregnancy complications, including gestational hypertension (19 %), intrauterine growth restriction (45 %), and preterm births (43 %). No significant improvement in live birth rate was observed among treated CIUE patients; however, caution is warranted when interpreting these findings due to the limited sample size. Future research in CIUE is crucial given its rarity and complexity., Competing Interests: Declaration of Competing Interest Dr. Mohamed A. Bedaiwy: Research grants from Canadian Institutes of Health Research (CIHR) and Ferring Pharmaceutical. He is on the advisory board for AbbVie, Pfizer, and Baxter. Other authors do not have any declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary., Aim: To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis., Methods: The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively., Results: We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups., Conclusion: FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Prolonged exposure to sun radiation may result in harmful skin photoaging. Therefore, discovering novel anti-photoaging treatment modalities is critical. An active component isolated from Salvia miltiorrhiza (SM), Salvianolic acid B (Sal-B), is a robust antioxidant and anti-inflammatory agent. This investigation aimed to discover the therapeutic impact and pathways of salvianolic acid B for UVB-induced skin photoaging, an area that remains unexplored., Methods: We conducted in vitro experiments on human dermal fibroblasts (HDFs) exposed to UVB radiation, assessing cellular senescence, superoxide dismutase (SOD) activity, cell viability, proliferation, migration, levels of reactive oxygen species (ROS), and mitochondrial health. The potential mechanism of Sal-B was analyzed using RNA sequencing, with further validation through Western blotting, PCR, and nuclear factor erythroid 2-related factor 2 (NRF2) silencing methods. In vivo, a model of skin photoaging induced by UVB in nude mice was employed. The collagen fiber levels were assessed utilizing hematoxylin and eosin (H&E), Masson, and Sirus red staining. Additionally, NRF2 and related gene and protein expression levels were identified utilizing PCR and Western blotting., Results: Sal-B was found to significantly counteract photoaging in UVB-exposed skin fibroblasts, reducing aging-related decline in fibroblast proliferation and an increase in apoptosis. It was observed that Sal-B aids in protecting mitochondria from excessive ROS production by promoting NRF2 nuclear translocation. NRF2 knockdown experiments established its necessity for Sal-B's anti-photoaging effects. The in vivo studies also verified Sal-B's anti-photoaging efficacy, surpassing that of tretinoin (Retino-A). These outcomes offer novel insights into the contribution of Sal-B in developing clinical treatment modalities for UVB-induced photodamage in skin fibroblasts., Conclusion: In this investigation, we identified the Sal-B protective impact on the senescence of dermal fibroblasts and skin photoaging induced by radiation of UVB. The outcomes suggest Sal-B as a potential modulator of the NRF2 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population., Methods: Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods., Results: The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p < 0.001), while obesity was linked to a 13.9% reduction in mortality risk (p < 0.001). The protective effect of obesity on mortality was similar in patients with (HR = 0.85) and without AF (HR = 0.86). AF led to a slightly higher risk of mortality in patients without obesity (HR = 1.16) compared to those with obesity (HR = 1.13). Kaplan-Meier survival curves highlighted that non-obese patients with AF had the lowest survival rate, whereas the highest survival was observed in obese patients without AF., Conclusions: AF significantly increased 1-year mortality risk in critically ill patients, whereas obesity was associated with a decreased mortality risk. The most adverse survival outcomes were identified in non-obese patients with AF., (© 2024. The Author(s).)

To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0-100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. PERSPECTIVE: This article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: The paravertebral muscles, characterized by their susceptibility to severe size loss and fat infiltration in old age, lack established reference values for age-related variations in muscle parameters. This study aims to fill this gap by establishing reference values for paravertebral muscles in a Chinese adult population., Materials and Methods: This cross-sectional study utilized the baseline data from the prospective cohort China Action on Spine and Hip (CASH). A total of 4305 community-dwelling participants aged 21-80 years in China were recruited between 2013 and 2017. Pregnant women, individuals with metal implants, limited mobility or diseases/conditions (spinal tumor, infection, etc.) affecting lumbar vertebra were excluded from the study. Psoas and paraspinal muscles were measured in quantitative computed tomography (QCT) images at the L3 and L5 levels using Osirix software. Age-related reference values for muscle area, density, and fat fraction were constructed as percentile charts using the lambda-mu-sigma (LMS) method., Results: The paravertebral muscles exhibited an age-related decline in muscle area and density, coupled with an increase in muscle fat fraction. Between the ages of 25 and 75, the reductions in psoas and paraspinal muscle cross-sectional area at the L3 level were - 0.47%/yr and - 0.53%/yr in men, and - 0.19%/yr and - 0.23%/yr in women, respectively. Notably, accelerated muscle loss was observed during menopause and postmenopause in women (45-75 years) and intermittently during middle and old age in men (35-55 and 60-75 years). Besides, the age-related decreases in PSMA, PMA, and PSMD and the increases in PSMFF were more pronounced in L5 than in L3 CONCLUSION: This study shows distinct patterns of accelerated muscle loss were identified in menopausal and postmenopausal women and in middle-aged and old men. The findings contribute valuable information for future investigations on paravertebral muscle loss and myosteatosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children., Methods: This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests., Results: 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm 2 , p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm 2 , p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively)., Conclusions: Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children., (© 2024. The Author(s).)

Background: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference., Case Summary: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory., Conclusion: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

As important components of soluble microbial products in water, nucleobases have attracted much attention due to the high toxicity of their direct aromatic halogenated disinfection by-products (AH-DBPs) during chlorination. However, multiple halogenation sites of AH-DBPs pose challenges to identify them. In this study, reaction sites of pyrimidine bases and nucleosides during chlorination were investigated by quantum chemical computational method. The results indicate that the anion salt forms play key roles in chlorination of uracil, thymine, and their nucleosides, while neutral forms make predominant contributions to cytosine and cytidine. In view of both kinetics and thermodynamics, C5 is the most reactive site for uracil and thymine, N3/C5 and N3 for respective uridine and thymidine, N1/C5/N 4 and N 4 for respective cytosine and cytidine, whose estimated apparent rate constants k obs-est of ∼10 3 , 10 3 /10 2 , 10 6 /10 2 /10 4 , and 10 3  M -1  s -1 , respectively, in consistent with the known experimental results. C6 in all pyrimidine compounds is hardly attacked by Cl + in HOCl ascribed to its positive charge, but readily attacked by OH‾ in hydrolysis and the N1=C6 bond was found to possess the highest reactivity in hydrolysis among all double bonds. In addition, the structure-kinetic reactivity relationship study reveals a relatively strong correlation between lgk obs-est and APT charge in all pyrimidine compounds rather than FED 2 (HOMO). The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility., Methods: The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk., Results: This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49-3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03-2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28-3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17-3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24-4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01-3.49) were associated with increased odds of infertility, respectively., Conclusion: There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility., (© 2024. The Author(s).)

Pituitary stalk interruption syndrome (PSIS) in female patients is mainly characterized by short stature, primary amenorrhea, absent or incomplete sexual maturation, and infertility. Successful pregnancies among these patients are rare. In this report, we describe a successful pregnancy and delivery in a 28-year-old Chinese woman with PSIS following in vitro fertilization and embryo transfer. The patient exhibited typical symptoms, including multiple pituitary hormone deficiency, typical triad signs in magnetic resonance imaging (MRI), undetectable serum gonadotropins and estradiol levels, and invisible antral follicles in both ovaries. During the first attempted controlled ovarian hyperstimulation cycle, 14 oocytes were retrieved and six embryos were acquired. Artificial endometrial preparation and frozen-thawed embryo transfer were performed, resulting in a clinical pregnancy after the transfer of a day 5 blastocyst. The patient was closely monitored throughout the pregnancy and multiple hormone dosages were modulated accordingly. She delivered a healthy boy by elective cesarean section, and the newborn developed normally during a 1-year follow-up period. This is the first report of a successful live birth in a woman with PSIS achieved through in vitro fertilization and frozen-thawed embryo transfer. A literature review on this topic is also presented., (© 2023 International Federation of Gynecology and Obstetrics.)

Resonant exchange of the chiral Majorana fermions (MFs) that is coupled to two parallel Majorana zero modes (MZMs) or two parallel quantum dots (QDs) is investigated. We find that, in the two QDs coupling case, the resonant exchange for the chiral MFs is analogous to that in the MZM coupling case. We further propose a circuit based on topological superconductor, which is formed by the proximity coupling of a quantum anomalous Hall insulator and a s-wave superconductor, to observe the resonant exchange of chiral MFs pairs. The numerical calculations show that the resonant transmission of the chiral MFs can be adjusted by varying the coupling parameters at superconductor phase differenceΔφ=π. It is particularly noteworthy that, by only modulating the coupling strength between the two QDs, the resonant exchange may be switched on or off. By adding another MZM, the non-Abelian braiding like operation can be realized. Therefore, our design scheme may provide another way for non-Abelian braiding operation of MFs and the findings may have potential application value in the realization of topological quantum computers., (© 2024 IOP Publishing Ltd.)

Study Question: Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)?, Summary Answer: Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth)., What Is Known Already: There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition., Study Design, Size, Duration: We conducted a population-based retrospective cohort study of 184 241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198 319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates., Participants/materials, Setting, Methods: Among individuals with at least two recorded live births between 2000 and 2018, 12 321 patients with RPL and 171 920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal-Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach., Main Results and the Role of Chance: The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09-4.58), 3.20 years (95% CI: 3.00-3.40), and 3.05 years (95% CI: 2.79-3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL., Limitations, Reasons for Caution: This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses., Wider Implications of the Findings: The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child., Study Funding/competing Interest(s): This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest., Trial Registration Number: NCT04360564., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4  kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15  keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1  MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Hypochlorous acid (HOCl) released from activated leukocytes plays a significant role in the human immune system, but is also implicated in numerous diseases due to its inappropriate production. Chlorinated nucleobases induce genetic changes that potentially enable and stimulate carcinogenesis, and thus have attracted considerable attention. However, their multiple halogenation sites pose challenges to identify them. As a good complement to experiments, quantum chemical computation was used to uncover chlorination sites and chlorinated products in this study. The results indicate that anion salt forms of all purine compounds play significant roles in chlorination except for adenosine. The kinetic reactivity order of all reaction sites in terms of the estimated apparent rate constant k obs-est (in M -1 s -1 ) is heterocyclic NH/N (10 2 -10 7 ) > exocyclic NH 2 (10 -2 -10) > heterocyclic C8 (10 -5 -10 -1 ), but the order is reversed for thermodynamics. Combining kinetics and thermodynamics, the numerical simulation results show that N9 is the most reactive site for purine bases to form the main initial chlorinated product, while for purine nucleosides N1 and exocyclic N 2 / N 6 are the most reactive sites to produce the main products controlled by kinetics and thermodynamics, respectively, and C8 is a possible site to generate the minor product. The formation mechanisms of biomarker 8-Cl- and 8-oxo-purine derivatives were also investigated. Additionally, the structure-kinetic reactivity relationship study reveals a good correlation between lg  k obs-est and APT charge in all purine compounds compared to FED 2 (HOMO), which proves again that the electrostatic interaction plays a key role. The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination.

Ischemic stroke is a common neurological disease. Currently, there are no Food and Drug Administration-approved drugs that can maximize the improvement in ischemic stroke-induced nerve damage. Hence, treating ischemic stroke remains a clinical challenge. Ferroptosis has been increasingly studied in recent years, and it is closely related to the pathophysiological process of ischemic stroke. Iron overload, reactive oxygen species accumulation, lipid peroxidation, and glutamate accumulation associated with ferroptosis are all present in ischemic stroke. This article focuses on describing the relationship between ferroptosis and ischemic stroke and summarizes the relevant substances that ameliorate ischemic stroke-induced neurological damage by inhibiting ferroptosis. Finally, the problems in the treatment of ischemic stroke targeting ferroptosis are discussed, hoping to provide a new direction for its treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

DNA is susceptible to various factors in vitro and in vivo and experience different forms of damage,among which double-strand break(DSB)is a deleterious form.To maintain the stability of genetic information,organisms have developed multiple mechanisms to repair DNA damage.Among these mechanisms,homologous recombination(HR)is praised for the high accuracy.The MRE11-RAD50-NBS1(MRN)complex plays an important role in HR and is conserved across different species.The knowledge on the MRN complex mainly came from the previous studies in Saccharomyces cerevisiae and Caenorhabditis elegans ,while studies in the last decades have revealed the role of mammalian MRN complex in DNA repair of higher animals.In this review,we first introduces the MRN complex regarding the composition,structure,and roles in HR.In addition,we discuss the human diseases such as ataxia-telangiectasia-like disorder,Nijmegen breakage syndrome,and Nijmegen breakage syndrome-like disorder that are caused by dysfunctions in the MRN complex.Furthermore,we summarize the mouse models established to study the clinical phenotypes of the above diseases.

Incorporating functional organic linkers into supertetrahedral chalcogenolate cluster-based materials is an effective synthetic strategy to expand structural diversity and generate tunable optical and photoelectric properties arising from synergistic effects. Herein, a mixed ligand engineering approach was adopted to design a supertetrahedral cluster-based assembled material [(Cd 6 Ag 4 (SPh) 16 (TPPA)(BPE) 0.5 )·2DMF] n (denoted as SCCAM-3) with a 2D bilayer architecture and broader visible-light absorption. Interestingly, SCCAM-3 demonstrates a long-lived afterglow at 83 K and efficient photocatalytic activity for degrading tetracycline in water.

Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria., Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED)., Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated., Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test., Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001)., Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes., Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained., Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we found that advanced oxidation protein products (AOPPs) in plasma were elevated in women with POI and had an adverse effect on granulosa cell proliferation. However, the mechanism underlying the effects of AOPPs on autophagy-lysosome pathway regulation in granulosa cells remains unclear. In this study, the effect of AOPPs on autophagy and lysosomal biogenesis and the underlying mechanisms were explored by a series of in vitro experiments in KGN and COV434 cell lines. AOPP-treated rat models were employed to determine the negative effect of AOPPs on the autophagy-lysosome systems in vivo. We found that increased AOPP levels activated the mammalian target of rapamycin (mTOR) pathway, and inhibited the autophagic response and lysosomal biogenesis in KGN and COV434 cells. Furthermore, scavenging of reactive oxygen species (ROS) with N-acetylcysteine and blockade of the mTOR pathway with rapamycin or via starvation alleviated the AOPP-induced inhibitory effects on autophagy and lysosomal biogenesis, suggesting that these effects of AOPPs are ROS-mTOR dependent. The protein expression and nuclear translocation of transcription factor EB (TFEB), the key regulator of lysosomal and autophagic function, were also impaired by the AOPP-activated ROS-mTOR pathway. In addition, TFEB overexpression attenuated the AOPP-induced impairment of autophagic flux and lysosomal biogenesis in KGN and COV434 cells. Chronic AOPP stimulation in vivo also impaired autophagy and lysosomal biogenesis in granulosa cells of rat ovaries. The results highlight that AOPPs lead to impairment of autophagic flux and lysosomal biogenesis via ROS-mTOR-TFEB signaling in granulosa cells and participate in the pathogenesis of POI., (© 2024. The Author(s).)

Background: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear., Methods: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods., Results: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress., Conclusion: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases., (© 2024. The Author(s).)

The conventional orthogonality of Laguerre-Gaussian (LG) beams is widely recognized and serves as the fundamental basis for mode division multiplexing utilizing LG beams as channels. However, this conventional orthogonality holds true only when two LG beams share the same axis. Whether non-coaxial LG beams, with parallel axes separated by a distance, are orthogonal to each other remains an open question. To address this issue and reveal the orthogonality of non-coaxial LG beams, we analytically derive the projection of one LG beam onto another. This projection exhibits a helical phase and a rotationally symmetric amplitude with dark rings present. These dark rings indicate that two non-coaxial LG beams are indeed orthogonal to each other when their axes are appropriately separated. Furthermore, any pair of non-coaxial LG beams within a set also exhibit orthogonality when their axes are fixed at a certain separation distance. This novel form of orthogonality predicts an innovative compound multiplexing technique that simultaneously combines mode and space, enabling more efficient packing of multiple LG beams within a single transmission aperture while maintaining parallel and closely spaced beam axes.

Background and Objective: Current methods for imaging reconstruction from high-ratio expansion microscopy (ExM) data are limited by anisotropic optical resolution and the requirement for extensive manual annotation, creating a significant bottleneck in the analysis of complex neuronal structures., Methods: We devised an innovative approach called the IsoGAN model, which utilizes a contrastive unsupervised generative adversarial network to sidestep these constraints. This model leverages multi-scale and isotropic neuron/protein/blood vessel morphology data to generate high-fidelity 3D representations of these structures, eliminating the need for rigorous manual annotation and supervision. The IsoGAN model introduces simplified structures with idealized morphologies as shape priors to ensure high consistency in the generated neuronal profiles across all points in space and scalability for arbitrarily large volumes., Results: The efficacy of the IsoGAN model in accurately reconstructing complex neuronal structures was quantitatively assessed by examining the consistency between the axial and lateral views and identifying a reduction in erroneous imaging artifacts. The IsoGAN model accurately reconstructed complex neuronal structures, as evidenced by the consistency between the axial and lateral views and a reduction in erroneous imaging artifacts, and can be further applied to various biological samples., Conclusion: With its ability to generate detailed 3D neurons/proteins/blood vessel structures using significantly fewer axial view images, IsoGAN can streamline the process of imaging reconstruction while maintaining the necessary detail, offering a transformative solution to the existing limitations in high-throughput morphology analysis across different structures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Diabetes, characterized as a well-known chronic metabolic syndrome, with its associated complications pose a substantial and escalating health and healthcare challenge on a global scale. Current strategies addressing diabetes are mainly symptomatic and there are fewer available curative pharmaceuticals for diabetic complications. Thus, there is an urgent need to identify novel pharmacological targets and agents. The impaired mitochondria have been associated with the etiology of diabetes and its complications, and the intervention of mitochondrial dysfunction represents an attractive breakthrough point for the treatments of diabetes and its complications. Natural products (NPs), with multicenter characteristics, multi-pharmacological activities and lower toxicity, have been caught attentions as the modulators of mitochondrial functions in the therapeutical filed of diabetes and its complications. This review mainly summarizes the recent progresses on the potential of 39 NPs and 2 plant-extracted mixtures to improve mitochondrial dysfunction against diabetes and its complications. It is expected that this work may be useful to accelerate the development of innovative drugs originated from NPs and improve upcoming therapeutics in diabetes and its complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze the contents of different kinds of fatty acids in carotid atherosclerotic plaques. Methods: A total of 24 patients who underwent carotid endarterectomy at the Second Affiliated Hospital of Naval Medical University from October 2021 to September 2022 due to moderate and severe carotid artery stenosis were retrospectively enrolled, including 20 males and 4 females, with a median age[ M ( Q 1 , Q 3 )] of 68.5 (63.5, 72.3) years. According to the symptoms of cerebral ischemia, the patients were divided into a symptomatic group (12 cases) and an asymptomatic group (12 cases). Regarding the pathological characteristics, the patients were divided into a stable group (14 cases) and a vulnerable group (10 cases) according to carotid plaque pathology scores. The expression differences of different types of fatty acids in carotid plaques were analyzed by targeted fatty acid metabolomics technology based on ultra-performance liquid chromatography-mass spectrometry (UPLC-ESI-MS/MS) analysis. Results: In the 24 samples, the median amount of fatty acids [ M ( Q 1 , Q 3 )] was 1 113 (330, 5 897) ng/g. A total of 13 medium and long-chain fatty acids were detected, including saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. The content of saturated fatty acids was 584 (290, 9 888) ng/g, accounting for the highest proportion of 51.8%. The content of polyunsaturated fatty acids was 1 444 (393, 4 264) ng/g, accounting for 44.4%. The content of monounsaturated fatty acids was 2 793 (1 558, 3 247) ng/g, accounting for 3.8%. The contents of linoleic acid, α-linolenic acid and oleic acid in carotid plaques in the symptomatic group were 1 760 (581, 3 006), 682 (527, 886) and 2 081 (1 358, 2 907) ng/g, respectively, which were lower than those in the asymptomatic group 3 149 (2 226, 4 683), 1 423 (964, 2 270) and 3 178 (2 352, 3 993) ng/g (all P <0.05). The contents of linoleic acid, α-linolenic acid and oleic acid in carotid plaques in the vulnerable group were 1 537 (588, 2 921), 649 (477, 850) and 2 081 (1 129, 2 831) ng/g, respectively, which were lower than those in the stable group 3 149 (2 047, 4 416), 1 423 (940, 2 184) and 3 091 (2 201, 3 973) ng/g (all P <0.05). There were no significant differences in the contents of 11, 14-eicosadienoic acid, γ-linolenic acid, eicosapentaenoic acid, arachidonic acid, erucic acid, margaric acid, pentadecanoic acid, stearic acid, dodecanoic acid and palmitic acid (all P >0.05). Conclusions: Saturated fatty acids are the main type in carotid plaques. The contents of oleic acid, α-linolenic acid and linoleic acid decrease in vulnerable plaques.

Neurological disorders affect a large population, often leading to different levels of disability and resulting in decreased quality of life. Due to the limited recovery obtained from surgical procedures and other medical approaches, a large number of patients with prolonged dysfunction receive neurorehabilitation protocols to improve their neural plasticity and regeneration. However, the poor neural regeneration ability cannot effectively rebuild the tissue integrity and neural functional networks; consequently, the prognoses of neurorehabilitation remain undetermined. To increase the chances of neural regeneration and functional recovery for patients with neurological disorders, regenerative rehabilitation was introduced with combined regenerative medicine and neurorehabilitation protocols to repair neural tissue damage and create an optimized biophysical microenvironment for neural regeneration potential. With the deepening of exosome research, an increasing number of studies have found that the systemic therapeutic effects of neurorehabilitation approaches are mediated by exosomes released by physically stimulated cells, which provides new insight into rehabilitative mechanisms. Meanwhile, exosome therapy also serves as an alternative cell-free therapy of regenerative medicine that is applied in partnership with neurorehabilitation approaches and formulates exosome-based neurological regenerative rehabilitation. In this study, we review the current state of exosome-associated neurorehabilitation. On the one hand, we focus on presenting the varied mediating effects of exosomes in neurorehabilitation protocols of specific neurological pathologies; on the other hand, we discuss the diverse combinations of exosome therapies and neurorehabilitation approaches in the field of neurological regenerative rehabilitation, aiming to increase the awareness of exosome research and applications in the rehabilitation of neurological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Plant-derived nucleic acids, especially small RNAs have been proved by increasing evidence in the pharmacological activities and disease treatment values in macrophage meditated anti-tumor performance, immune regulating functions and antiviral activities. But the uptake, application and delivery strategies of RNAs as biodrugs are different from the small molecules and recombinant protein drugs. This article summarizes the reported evidence for cross-kingdom regulation by plant derived functional mRNAs and miRNAs. Based on that, their involvement and potentials in macrophage-mediated anti-tumor/inflammatory therapies are mainly discussed, as well as the load prospect of plant RNAs in viruses and natural exosome vehicles, and their delivery to mammalian cells through macrophage were also summarized. This review is to provide evidence and views for the plant derived RNAs as next generation of drugs with application potential in nucleic acid-based bio-therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Chen, Zhang, Yan, Yan, Zhu and Peng.)

Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni 0.85 Se/MoSe 2 heterostructural electrocatalyst, Mo x -Ni 0.85 Se/MoSe 2 , was successfully prepared by simultaneously doping Mo cations into the Ni 0.85 Se lattice (Mo x -Ni 0.85 Se) and growing atomic MoSe 2 nanosheets epitaxially at the edge of the Mo x -Ni 0.85 Se. Such an Mo x -Ni 0.85 Se/MoSe 2 catalyst requires only 110 mV to drive current densities of 10 mA cm -2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm -2 . The experimental results, combined with the density functional theory calculations, reveal that the Mo x -Ni 0.85 Se/MoSe 2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni 0.85 Se can regulate the local electronic configuration of the Mo x -Ni 0.85 Se/MoSe 2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mo x -Ni 0.85 Se/MoSe 2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Objectives: To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE)., Methods: Stool samples from 78 treatment-naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment-naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment., Results: The gut microbiota of treatment-naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to healthy controls., Conclusions: The gut microbiota in treatment-naïve pSS patients was disturbed and shared significant similarity with that in SLE patients., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the odds of developing adverse maternal and perinatal outcomes in primiparous singleton pregnancies conceived with assisted reproductive technology (ART) compared with pregnancies conceived without ART., Study Design: A retrospective population-based cohort study using data from the British Columbia Perinatal Data Registry. The population included primiparous women with singleton live or stillbirths delivering at or after 20 weeks' gestation between April 1st 2008-March 31st, 2021. Women who conceived with ART were compared with those who conceived without ART. The main outcome measures were gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, neonatal intensive care unit admission, stillbirth, and 5-minute Apgar score. Adjusted odds ratios were calculated., Results: The study population included 191,059 primiparous women: 183,819 conceived without ART, 7,240 conceived using ART. After controlling for age, body mass index, pre-gestational diabetes, and smoking status, singleton pregnancies conceived by ART had significantly higher odds of gestational diabetes (OR 1.18, 95 % confidence interval [CI] 1.10-1.26) and hypertensive disorders of pregnancy (OR 1.39, 95 % CI 1.29-1.51). There were also significantly increased odds of preterm birth (OR 1.35, 95 % CI 1.25-1.46), low birth weight (OR 1.35, 95 % CI 1.23-1.49), and neonatal intensive care unit admission (OR 1.21, 95 % CI 1.11-1.32). There was not a statistically significant difference in the odds of stillbirth (OR 1.06, 95 % CI 0.72-1.57) or 5-minute Apgar score < 7 (OR 1.10, 95 % CI 0.97-1.26)., Conclusion: There is an increased odds of developing several adverse maternal or neonatal outcomes in primiparous singleton pregnancies conceived by ART including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, and increased incidence of neonatal intensive care unit admissions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Study Objective: To study the impact of Müllerian anomalies on reproductive outcomes in a recurrent pregnancy loss (RPL) population and to evaluate the effect of surgical correction of uterine septum on the odds of achieving live birth in RPL patients with a septate uterus., Design: A retrospective cohort study., Setting: A specialized RPL clinic at a tertiary center., Patients: RPL patients with ≥ 2 pregnancy losses before 20 weeks' gestation who attended a specialized RPL clinic., Intervention: We aimed to assess the association between a possible risk factor (Müllerian anomalies) and reproductive outcomes and that between having surgery for septate uterus and achieving a live birth., Measurements and Main Results: The primary outcome is live birth rate in RPL patients with Müllerian anomalies compared with those without; secondary outcome measures include rates of full-term live birth, preterm live birth, first and second trimester pregnancy loss, and stillbirth. After adjusting for patient age at the initial RPL visit, the number of pregnancy losses, and the presence of any other abnormal RPL investigation, the odds of achieving live birth were on average 49.4% lower for patients with a septate uterus than those without Müllerian anomalies (odds ratio, 0.51; 95% confidence interval, 0.30-0.86) in the studied cohort (n = 377). A subanalysis of 72 patients with septate uterus demonstrated a higher likelihood of live birth in those who underwent septum resection (46/72; 63.9%) than those who elected to go for expectant management (26/72; 36.1%), yet this study was underpowered to establish a significant difference (52.2% vs 34.6%; p = .22)., Conclusion: In RPL patients, having a septate uterus significantly decreased the chances of achieving live birth. Patients with septate uterus who received hysteroscopic septum division had a higher tendency to achieve more live births than those who elected expectant management. However, our study was underpowered to detect a statistically significant difference., (Copyright © 2023 AAGL. All rights reserved.)

Introduction: We propose a standardized protocol for measurement of nerve bundle density in endometriosis as a potential biomarker, including in deep endometriosis (DE), ovarian endometriomas (OMA) and superficial peritoneal endometriosis (SUP)., Methods: This was a prospective cohort of surgically excised endometriosis samples from Dec 1st 2013 and Dec 31st 2017 at a tertiary referral center for endometriosis in Vancouver, BC, Canada. Surgical data were available from linked patient registry. Protein gene product 9.5 (PGP9.5) was used to identify nerve bundles on immunohistochemistry. PGP9.5 nerve bundles were counted visually. To calculate nerve bundle density, PGP9.5 nerve bundle count was divided by the tissue surface area (total on the slide). All samples were assessed using NHS Elements software for semi-automated measurement of the tissue surface area. For a subset of samples, high power fields (HPFs) were also counted as manual measurement of the tissue surface area. Intraclass correlation was used to assess intra observer and inter observer reliability. Generalized linear mixed model (GLMM) with random intercepts only was conducted to assess differences in PGP9.5 nerve bundle density by endometriosis type (DE, OMA, SUP)., Results: In total, 236 tissue samples out of 121 participants were available for analysis in the current study. Semi-automated surface area measurement could be performed in 94.5% of the samples and showed good correlation with manually counted HPFs (Spearman's rho = 0.781, p  < 0.001). To assess intra observer reliability, 11 samples were assessed twice by the same observer; to assess inter observer reliability, 11 random samples were blindly assessed by two observers. Intra observer reliability and inter observer reliability for nerve bundle density were excellent: 0.979 and 0.985, respectively. PGP9.5 nerve bundle density varied among samples and no nerve bundles could be found in 24.6% of the samples. GLMM showed a significant difference in PGP9.5 nerve bundle density between the different endometriosis types (X 2  = 87.6, P  < 0.001 after adjusting for hormonal therapy, with higher density in DE and SUP in comparison to OMA)., Conclusion: A standardized protocol is presented to measure PGP9.5 nerve bundle density in endometriosis, which may serve as a biomarker reflecting local neurogenesis in the endometriosis microenvironment., Competing Interests: MK is a consultant for Helix Biopharma, which has no relation to the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zoet, Tucker, Orr, Alotaibi, Liu, Noga, Köbel and Yong.)

Dichloroacetonitrile (DCAN) as one of the potentially prioritized regulated DBPs has drawn great attention; however, understanding its formation, especially the C-C bond cleavage mechanisms, is limited. In this study, DCAN formation mechanisms from long-chain primary amines, amino acids, and dipeptides during chlorination were investigated by a combined computational and experimental approach. The results indicate that nitriles initially generate for all of the above precursors, then they undergo β- C -hydroxylation or/and α- C -chlorination processes, and finally, DCAN is produced through the C α -C β bond cleavage. For the first time, the underlying mechanism of the C-C bond cleavage was unraveled to be electron transfer from the O - anion into its attached C atom in the chlorinated nitriles, leading to the strongly polarized C α -C β bond heterocleavage and DCAN - formation. Moreover, DCAN molar yields of precursors studied in the present work were found to be determined by their groups at the γ-site of the amino group, where the carbonyl group including -CO 2 - , -COR, and -CONHR, the aromatic group, and the -OH group can all dramatically facilitate DCAN formation by skipping over or promoting the time-consuming β- C -hydroxylation process and featuring relatively lower activation free energies in the C-C bond cleavage. Importantly, 4-amino-2-hydroxybutyric acid was revealed to possess the highest DCAN yield among all the known aliphatic long-chain precursors to date during chlorination. Additionally, enonitriles, (chloro-)isocyanates, and nitriles can be generated during DCAN formation and should be of concern due to their high toxicities.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by cessation of menstruation occurring before the age of 40 years. The genetic causes of idiopathic POI remain unclear. Here we recruited a POI patient from a consanguineous family to screen for potential pathogenic variants associated with POI. Genetic variants of the pedigree were screened using whole-exome sequencing analysis and validated through direct Sanger sequencing. A homozygous variant in TUFM (c.524G>C: p.Gly175Ala) was identified in this family. TUFM (Tu translation elongation factor, mitochondrial) is a nuclear-encoded mitochondrial protein translation elongation factor that plays a critical role in maintaining normal mitochondrial function. The variant position was highly conserved among species and predicted to be disease causing. Our in vitro functional studies demonstrated that this variant causes decreased TUFM protein expression, leading to mitochondrial dysfunction and impaired autophagy activation. Moreover, we found that mice with targeted Tufm variant recapitulated the phenotypes of human POI. Thus, this is the first report of a homozygous pathogenic TUFM variant in POI. Our findings highlighted the essential role of mitochondrial genes in folliculogenesis and ovarian function maintenance., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with β-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

Titanium dioxide photocatalysts can break down pollutants using natural light. They possess notable light stability, chemical stability, and catalytic effects, thus leading to extensive research worldwide. However, the limited light absorption range of titanium dioxide and their inefficiencies in generating and transporting photogenerated carriers hinder the enhancement of their photocatalytic performance. In this study, we employ a femtosecond laser composite processing method to create an Ag-TiO 2 nanoplate composite catalyst. This method doubles the catalytic efficiency compared with the structure processed solely with the femtosecond laser. The resulting Ag-TiO 2 nanoplate composite catalysts show significant promise for addressing environmental and energy challenges, including the photodegradation of organic pollutants.