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Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship are unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but their role in GAON is unclear. This study aimed to explore the connection between GAON and gut microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 gut microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated with GAON. RNA-seq analysis revealed that GAON differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared patients who developed GAON (17 cases), those who did not (GAnON, 15 cases), and those untreated with GCs (Blank, 15 cases) for gut microbiota composition, short-chain fatty acids (SCFAs), and serum inflammatory factors. Our findings indicated a decrease in Lachnospiraceae abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) in GC-treated patients. Serum inflammatory factors (IL-17 A, IL-33, and TNF-α) associated with GAON (59.603 ± 12.147, 89.337 ± 20.714, 42.584 ± 9.185) showed significant differences between Blank (1.446 ± 0.683, 11.534 ± 4.705, 4.682 ± 1.48) and GAnON (25.353 ± 8.181, 32.527 ± 7.352, 12.49 ± 3.217) groups, with a negative correlation between these factors and Lachnospiraceae levels. Butyric acid levels in SCFAs varied among groups (P<0.01) and correlated with Lachnospiraceae and inflammatory factors. Controlled experiments in GAON rats demonstrated butyric acid's osteoprotective role in GAON development (P<0.01). In conclusion, our study suggests that reduced Lachnospiraceae and butyric acid levels, along with increased inflammation due to GCs use, contribute to GAON. Butyric acid may mediate the effects of Lachnospiraceae and inflammation. Butyrate supplementation could potentially reduce GAON incidence, offering a novel approach for its clinical management., Competing Interests: Declarations Ethics approval and consent to participate Sample collection was approved by the Ethics Committee at Jiangsu Provincial Hospital of Traditional Chinese Medicine (No. 2023NL-037-01). All volunteers voluntarily donated their own discarded femoral head specimens, stools, blood and signed an informed consent form. All animal experiments were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine (202306A059), and were conducted according to the National Research Council Guide for Care and Use of Laboratory Animals. Competing interests No potential conflict of interest was reported by the author(s)., (© 2024. The Author(s).)

Background: Aromatase inhibitors (AIs) are commonly used to treat postmenopausal hormone receptor positive breast cancer, but there is currently a lack of comprehensive safety reports on AIs in large-scale cohorts., Research Design and Methods: We conducted a retrospective pharmacovigilance survey based on the FDA Adverse Event Reporting System, retrieving relevant reports from the 2004 to the 2023, aiming to conduct a comprehensive comparative analysis of adverse reactions associated with AIs. In addition, we elucidated the potential toxicological mechanisms of AIs related adverse events through functional enrichment analysis., Results: A total of 7,933 adverse event reports related to AIs were collected, and there were 642 positive signals at the preferred term level. The top three signal intensities for anastrozole are: antiphospholipid syndrome, plantar fasciitis and autoimmune pancreatitis. The top three signal intensities for letrozole are: androgenetic alopecia and myosclerosis, pneumonic herpes virus. The top three signal intensities for exemestane are: infection reactivation, thyroxine free decreased and dilatation atrial. In terms of onset time, letrozole has the earliest onset time overall, followed by exemestane, and finally anastrozole., Conclusions: Our research corroborates the typical adverse events linked to AIs while highlighting potential safety concerns in their real-world clinical application.

Solar-driven interfacial evaporation has emerged as a promising avenue for clean water production, leveraging solar energy to extract water vapor from salty and polluted water sources. However, a critical challenge remains, during the photothermal evaporation process, organic pollutants and small water-soluble molecules can transfer into distilled steam, degrading the purity of the collected water. Herein, we develop a multifunctional clean water generation system that integrates photothermal conversion, adsorptive filtration and subsequent photocatalytic purification within a unified platform. This system features an inner hierarchical porous metal-carbon layer derived from ZIF-67 carbonization, seamlessly bridging a wood carbon scaffold and BiOBr nanosheets (BiOBr@ZCW) to smoothly facilitate synergistic actions between photothermal evaporation and adsorption-photodegradation processes. This BiOBr@ZCW configuration not only minimizes thermal dissipation, facilitating a high evaporation rate of 1.67 kg m -2 h -1 and an efficiency of 85% under standard solar irradiation but also enhances the photocatalytic degradation of the rhodamine B organic pollutant with a remarkable 98.43% degradation rate within just 20 minutes. This integrated system offers a robust solution to the challenges of water purification by ensuring both high efficiency in solar steam generation and effective pollutant degradation.

Conventional mini percutaneous nephrolithotomy (mPCNL) typically necessitates the pre-operative placement of ureteral catheters. With the development of enhanced recovery after surgery (ERAS), we introduce a novel approach: no ureteral catheter mini percutaneous nephrolithotomy (NUC-mPCNL). To evaluate the efficacy and safety of this innovative procedure compared to mPCNL, we compared the total operative time, stone clearance rate (SCR), stone-free rate (SFR), and complications among patients undergoing either modality from January to September 2021. Our findings revealed a statistically significant reduction in the mean total operative time for the NUC-mPCNL group (42.6 ± 2.4 vs. 60.2 ± 3.4 min, p < 0.001). The SCR, SFR and CSFR were comparable between two groups (98.5% vs. 97.8%, 84.3% vs. 76.0%, 64.7% vs. 60.0%, p = 0.337, 0.295, 0.625). WBC rise, hemoglobin drop and neutrophil percentage rise were similar in both groups. The overall complication rate in the NUC-mPCNL group was lower; however, the difference was not statistically significant (Clavien I, II and III; 11 vs. 13, 1 vs. 2 and 1 vs. 1). Consequently, we conclude that NUC-mPCNL effectively shortens the operative time and holds potential for expedited postoperative recovery., (© 2024. The Author(s).)

Objective: To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve. Methods: The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People's Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method . Results: Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P >0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t= 2.38, P= 0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t= 8.77, P =0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t= 6.96, P= 0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t= 3.43, P= 0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t= 4.58, P= 0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t= 2.43, P =0.007; DID for plum blossom pile bean clamping=58.42, t= 3.03, P= 0.013; DID for ferrule positioning=28.33, t =2.83, P =0.031; DID for threading with both hands=48.89, t= 2.10, P= 0.042; DID for sewing and knotting=54.78, t= 3.57, P= 0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs . 4 class hours; ferrule positioning: 4 class hours vs . 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t =-2.85, P =0.004; threading with both hands: t =-2.66, P= 0.008). Conclusion: The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Ethanol isa promising energy vector for closing the anthropogenic carbon cycle through reversible electrochemical redox. Currently, ethanol electrosynthesissuffers from low product selectivity due to the competitive advantage of ethylene in CO 2 /CO electroreduction. Here, a facet-selective metal-doping strategy is reported, tuning the reaction kinetics of CO reduction paths and thus enhancing the ethanol selectivity. The theoretical calculations reveal that nickel (Ni)doped Cu(100) surface facilitates water dissociation to form adsorbed hydrogen, which promotesselective electrochemical hydrogenation of a key C 2 intermediate ( * CHCOH) toward ethanol path over ethylene path. Experimentally, a solution-phase synthesis of a Ni-doped {100}-dominated Copper nanowires (Cu NWs) catalyst is reported, enabling an ethanol Faradaic efficiency of 56% and a selectivity ratio of ethanol to ethylene of 2.7, which are ≈4 and 15 times larger than those of undoped Cu NWs, respectively. The operando spectroscopic characterizations confirm that Ni-doping in Cu NWs can alter the interfacial water activity and thus regulate the C 2 product selectivity. With further electrode engineering, a membrane electrode assembly electrolyzer using Ni-doped Cu NWs catalysts demonstrates an ethanol Faradaic efficiency over 50% at 300 mA cm -2 with a full cell voltage of ≈2.7 V and operates stably for over 300 h., (© 2024 Wiley‐VCH GmbH.)

Black nightshade (Solanum nigrum L.) belongs to Solanaceae family, which is distributed all over China and has become one of the malignant weeds in cotton field in Xinjiang (Zhang et al., 2020; Zhang et al., 2021). During July 2016 to August 2023, leaf spot was observed on black nightshade in Hami and Shihezi city, Xinjiang, China. The spots appeared as brown circular or irregular, with some small black dots surrounded with yellow halos. Twenty five black nightshade plants were collected from a cotton field (100 m2) for pathogen isolation in Shihezi, July 2023. Leaf samples (2×2 mm) from the boundary between diseased tissue and healthy tissue, sterilized in 70% ethanol for 45 s, dipped in 2% NaClO for 30 s, rinsed three times with sterile distilled water, placed on potato dextrose agar (PDA) after dried and cultivated at 25°C in the dark for 4 days. Twenty-five fungal isolates were obtained and purified by using the single-spore isolation method, and all isolates were found to be similar in morphology, appeared as dark brown and produced dark brown pigmentation on PDA. Conidiophores were black brown, 8 to 58 × 10 to 20 μm, with 1 to 5 transverse septa and 0 to 3 longitudinal septa, the results similar to those of Alternaria alternata isolated from buckwheat (Li et al., 2021). To confirm this identification, total genomic DNA of the isolates were extracted by CTAB method (Doyle et al., 1987). The internal transcribed spacer (rDNA-ITS), Alternaria major allergen gene (Alt α1) and glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) of the A. alternata 26 were amplified using the primers ITS1/ITS4 (Glass et al., 1995), Altα1-F/Altα1-R (Li et al., 2024) and gpd-F/gpd-R (5'-CAACGGCTTCGGTCGCAT- TG-3' / 5'-GCCAAGCAGTTGGTTGTG-3'), respectively. The rDNA-ITS, Altα1 and GAPDH gene sequences were deposited in GenBank (KX904867, PP263361, PP263360), and showed 100% identity (rDNA-ITS: 572 out of 609 bp; Alt α1: 514 out of 516 bp; GAPDH: 619 out of 619 bp) to A. alternata (KU179665; MW522975; MK451977), respectively. The multi-gene phylogenetic tree showed that the representative isolate was grouped with A. alternata and identified as A. alternata. Black nightshade was used for pathogenicity assay. Fifteen plants at 3 to 4-leaf stage were selected and sprayed with the conidial suspension (1.0×106 spores/mL) of A. alternata 26 after wound the underside of leaves (2 mm length) with inoculating needle. Five plants were sprayed with sterilized water as control. After inoculation, placed the plants in a plastic box and covered with plastic wrap to keep 80% relative humidity for 3 days at 25℃ in the greenhouse, then removed the plastic box. Symptoms of leaf spots appeared within 12 - 15 days that were similar to the symptoms observed in the field, and the fungal pathogen that was re-isolated from symptomatic leaves was identical to original pathogen on the basis of morphological and molecular analysis to fulfill Koch's postulates. This experiment was repeated three times, and the disease incidence was above 80% after inoculation at each time. To our knowledge, this is the first report of A. alternata causing leaf spot of black nightshade in China. This report will help us to monitoring distribution of the disease and providing theoretical basis for disease prevention and control.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no interests to declare.

Background: X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis., Case Presentation: A G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM&#95;000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2&#95;Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae., Conclusion: A novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1., (© 2024. The Author(s).)

Background: The aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed., Methods: The expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. In vitro experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings in vivo using xenograft tumors. Tumor cell lines were developed to study AEG-1's effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns., Results: Our analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis., Conclusion: In conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy., 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 © 2024 Yao, Liu, Xu, Xi, Lin, Piao, Liu, Guo and Wang.)

Introduction: The aim of the study was to explore the relationship between the dilation states of the renal collecting system in flexible ureteroscopy (f-URS) view and intrarenal pressure (IRP)., Methods: Fifteen porcine kidneys were randomly selected and numbered 1 through 15. Pressure transducers were inserted into the renal calyx via puncture and adjusted to a zero position. The distal end of the f-URS probe was placed within the renal pelvis. Perfusion rates of 50 mL/min, 80 mL/min, and 100 mL/min were utilized. We observed the relationship between the dilation state of the renal collecting system and changes in IRP. The state of complete dilation was defined as an unchanging spatial morphology of the renal collecting system as visualized during f-URS., Results: With irrigation rates of 50 mL/min, 80 mL/min, and 100 mL/min, IRP values at the moment of complete dilation of the renal collecting system ranged from 16 to 18 cm H2O, 16-19 cm H2O, and 16-19 cm H2O, respectively. Maximum IRPs ranged from 47 to 49 cm H2O, 82-85 cm H2O, and 97-100 cm H2O, respectively. Prior to complete dilation of the renal collecting system, IRP consistently remained below 20 cm H2O. However, following full dilation of the renal collecting system, IRP rose rapidly and rapidly surpassed 20 cm H2O. Despite sustained elevations in IRP following full dilation, no significant alterations in the renal collecting system dilated morphological were observed with f-URS., Conclusions: In vitro experiments indicate that when the renal collecting system is not fully dilated, the IRP is consistently less than 20 cm H2O. Evaluation of IRP being within a safe range can be determined by assessing the dilation status of the renal collecting system., (© 2024 S. Karger AG, Basel.)

A stable solid-electrolyte interphase (SEI) is crucial for cycling reversibility of Na-ion batteries by mitigating continuous side reactions. So far, the severe SEI dissolution leads to low Coulombic efficiency (CE) and short cycle life. Meanwhile, the quantified relationship between SEI components and their solubility remains unclear. In this work, we establish the direct correlation between SEI components and SEI solubility, and quantify that the solubility of organic-rich SEI is 3.26 times of inorganic-rich SEI. We further propose a feasible strategy to preform inorganic-rich insoluble SEI and demonstrate a practical hard carbon (HC)||NaMn 0.33 Fe 0.33 Ni 0.33 O 2 full cell in a commercial electrolyte of 1 M NaPF 6 in propylene carbonate (PC) with 80.0 % capacity retention for 900 cycles, and achieve a record-high average CE of 99.95 % for a practical Na-ion full cell. This study provides an effective strategy of preforming insoluble SEI to suppress its dissolution towards highly reversible Na-ion batteries., (© 2024 Wiley-VCH GmbH.)

To explore the characteristics of pediatric primary retroperitoneal teratoma and the influencing factors of perioperative complications. The clinical data, imaging data, pathology results, perioperative complications, etc of patients with primary retroperitoneal teratoma admitted and treated at Shanxi Children ' s Hospital from March 2013 to September 2023 were retrospectively analyzed. The patients were divided into no complication group and complication group according to whether there were perioperative complications. The differences between the two groups were compared, and the influencing factors of complications were analyzed by multivariate logistic regression model. A total of 33 patients were included in this study, including 7 males and 26 females, with an age of [ M ( Q 1 , Q 3 ), 9.0 (4.0, 24.0)] months. Nineteen cases had tumors located in the left upper abdomen and 14 cases in the right upper abdomen, among which 17 cases grew across the midline, with the maximum tumor diameter of (12.9±4.5) cm. All patients had anatomical displacement of retroperitoneal vessels and organs: the number of anatomical displaced arteries was 3 (3, 4), the number of anatomical displaced veins was 4 (3, 5), the number of anatomical displaced organs was 5 (4, 6). Pathologic examination revealed 28 mature teratomas (Grade 0 and Grade 1) and 5 immature teratomas (Grade 2 and Grade 3). There were 18 cases in no complication group and 15 cases in the complication group. The incidence of perioperative complications was 45.5% (15/33). The number of tumors crossing the midline (6/18 vs 11/15, P =0.037), the number of tumors adhering closely to the surrounding tissues (7/18 vs 12/15, P =0.033), the number of anatomical displaced veins [4 (3, 4) vs 5 (4, 5), P =0.001], and the number of anatomical displaced organs [4 (3, 5) vs 6 (5, 6), P =0.001] were significantly different between the two groups. Multivariate logistic regression model analysis showed that the number of anatomical displaced organs ( OR =8.781, 95% CI : 2.155-35.784, P =0.002) was the influencing factor for perioperative complications of pediatric primary retroperitoneal teratoma.

Spectrum sensing (SS) technology is essential for cognitive radio (CR) networks to effectively identify and utilize idle spectrum resources. Due to the influence of noise characteristics in the channel, providing accurate sensing results is challenging. In order to improve the performance of SS under non-Gaussian noise and overcome the limitations of existing methods that are mostly based on a single feature, we propose a novel time-frequency cross fusion network (TFCFN). Specifically, we utilize gated recurrent units (GRU) to capture long-term dependencies in the time domain on the original signals, meanwhile, we perform a fast Fourier transform (FFT) on the original signals to obtain the frequency domain information, and subsequently use convolutional neural networks (CNN) to extract the local spatial features in the frequency domain. Ultimately, these time-domain and frequency-domain features are dynamically fused through a cross-attention mechanism to construct more comprehensive and robust features for signal classification. We use generalized Gaussian distribution (GGD) as the noise model and reconstruct the RadioML2016.10a dataset to explore the performance under various noise conditions. The experimental results show that compared with the baseline methods, TFCFN exhibits better detection ability and maintains lower complexity in both Gaussian and non-Gaussian noise environments. Notably, when the shape parameter of GGD is set to 0.5 and the signal-to-noise ratio (SNR) of the received signal is -16dB, it can maintain the probability of false alarm ( P f ) of 10% while still ensuring the probability of detection ( P d ) of over 90%., (© 2024. The Author(s).)

Polycrystalline lead halide perovskite finds promising use in fabricating X-ray detectors with a large lateral size, adjustable thickness, and diverse synthesis processes. However, a large dark current hinders its development for weak signal detection. Herein, we propose a multistep pressing strategy for manufacturing a CsPbBr 3 /CsPbCl 3 heterojunction wafer for a reduced dark current X-ray detector, and the device keeps a high sensitivity value after the insertion of a barrier by heterojunction; thus, the trade-off between sensitivity and dark current can be broken. The X-ray detector with a metal-semiconductor-metal structure yields a sensitivity of 6.32 × 10 4 μC Gy air -1 cm -2 at a bias of 12 V, a 1/ f noise of 1.02 × 10 -13 A/Hz -1/2 , and a detection limit of 66.58 nGy s -1 . These performance parameters are considerably better than those of a similar X-ray detector based on the single-structure wafer. The improved device performance of the heterostructure X-ray detector is ascribed to the suppressed carrier recombination, enhanced carrier transportation of the heterojunction, and strong X-ray attenuation of the CsPbCl 3 layer. The pixel array device is further used in imaging applications. Hence, this study provides an efficient strategy for fabricating heterostructure polycrystalline lead halide perovskite wafers for use in high-performance wafer-based X-ray detectors.

Ten previously undescribed dammarane-type triterpenoid glycosides, cyclocarysaponins A-J (1-10), were isolated from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja. The structures of these compounds were characterized through detailed spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The cytotoxic activities of all isolates were assessed against five human cancer cell lines (Bel-7402, Caski, BGC-823, A2780, and HCT-116). Of the tested compounds, compounds 1, 7, and 9 exhibited selective cytotoxicity against one or more human cancer cell lines., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the anatomical complexity of the left atrial appendage (LAA) using fractal dimension (FD) based on cardiac computed tomography angiography (CTA) and the association between LAA FD and LAA thrombosis., Materials and Methods: Patients with atrial fibrillation (AF) who underwent both cardiac CTA and transesophageal echocardiography (TEE) between December 2018 and December 2022 were retrospectively analyzed. Patients were categorized into normal (n = 925), circulatory stasis (n = 82), and thrombus groups (n = 76) based on TEE results and propensity score matching (PSM) was performed for subsequent analysis. FD was calculated to quantify the morphological heterogeneity of LAA. Independent risk factors for thrombus were screened using logistic regression. The diagnostic performance of FD and CHA 2 DS 2 -VaSc score for predicting thrombus was evaluated using the area under the receiver operating characteristics curve (AUC)., Results: LAA FD was higher in the thrombus group (1.61 [1.49, 1.70], P < 0.001) than in the circulatory stasis (1.33 [1.18, 1.47]) and normal groups (1.30 [1.18, 1.42]) both before and after PSM. LAA FD was also an independent risk factor in the thrombus (OR [odds ratio] = 570,861.15 compared to normal, 41,122.87 compared to circulatory stasis; all P < 0.001) and circulatory stasis group (OR = 98.87, P = 0.001) after PSM. The diagnostic performance of LAA FD was significantly better than the CHA 2 DS 2 -VaSc score in identifying thrombus., Conclusions: Patients with high LAA FD are more likely to develop LAA thrombus, and the use of FD provides an effective method for assessing the risk of thrombosis in AF patients, thereby guiding individualized clinical treatment., 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 Inc. All rights reserved.)

Transient receptor potential melastatin (TRPM) channels have emerged as potential therapeutic targets for cerebral ischemia-reperfusion (I/R) injury. We highlight recent findings on the involvement of TRPM channels in oxidative stress, mitochondrial dysfunction, inflammation, and calcium overload. We also discuss the challenges and future directions in targeting TRPM channels for cerebral I/R injury., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Retinal detachment (RD) is a sight-threatening condition that occurs in several retinal diseases. Microglia that reside in retina are activated after RD and play a role in the death of photoreceptor cells. The involvement of microglial pyroptosis in the early pathological process of RD is still unclear. VX-765, an inhibitor of caspase-1, may exert neuroprotective effects by targeting microglial pyroptosis in nervous system disease; however, whether it plays a role in RD is uncertain. This study detected and localized pyroptosis to specific cells by immunofluorescence co-staining and flow cytometry in rat RD models. The majority of gasdermin D N-terminal (GSDMD-N)-positive cells exhibited IBA1-positive or P2RY12-positive microglia in the early stage of RD, indicating the pyroptosis of microglia. Administration of VX-765 shifted the microglia phenotype from M1 to M2, inhibited microglial migration toward the outer nuclear layer (ONL) post-RD, and most importantly, inhibited microglial pyroptosis. The thickness of ONL increased with VX-765 administration, and the photoreceptors were more structured and orderly under hematoxylin and eosin staining and transmission electron microscopy, revealing the protective effects of VX-765 on photoreceptors. Overall, this study demonstrated that inflammation induced by pyroptosis of microglia is the early pathological process of RD. VX-765 may serve as a candidate therapeutic approach for the treatment of RD by targeting microglia., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti 3 C 2 T x MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH 2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti 3 C 2 T x -APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m -2  h -1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm 2 ) evaporator, and the evaporation rate is further increased to 1.672 kg m -2  h -1 for a small-area (2 × 2 cm 2 ) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h -1 /$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene., 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 Inc. All rights reserved.)

Efficient removal and recovery of phosphorus from aquaculture tailwater is challenging due to increasing strict water environment restrictions. This study presents a sustainable approach by using microalgae-waste-derived hydrogels/membranes for phosphorus adsorption and microalgae cultivation. Waste from Euglena gracilis (or Haematococcus pluvialis), modified with magnesium, was converted into biochars (abbreviated as MEBC or MHBC). This biochars were then combined with sodium alginate to fabricate hydrogels and with polyvinyl chloride to create membranes. Due to the almost 100 % phosphorus removal of MEBC (or MHBC) biochar, the as-obtained hydrogels/membranes demonstrated excellent phosphate adsorption, reducing total phosphorus in real aquaculture tailwater from 11 mg/L to 0. Additionally, the phosphorus-saturated hydrogel served as a phosphorus source for microalgae cultivation, while the membranes facilitated microalgae harvesting with a water flux over 40 L/m 2 /h. This study provides an eco-friendly solution for using microalgae-waste-derived materials to effectively address phosphorus removal and recovery challenges in aquaculture tailwater., 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. Published by Elsevier Ltd.)

Background: Low serum ceruloplasmin concentration is considered robust marker for Wilson disease (WD) screening, measuring serum ceruloplasmin oxidase activity might be an even more valuable diagnostic tool, but it has not been sufficiently studied., Methods: All patients who were assessed for serum ceruloplasmin oxidase activity between January 1, 2016, and September 2, 2019, were enrolled in this study. The diagnostic performance of serum ceruloplasmin oxidase activity was analyzed using receiver operating characteristic curve analysis (ROC), Spearman's rank correlation, and Mann-Whitney U test., Results: Serum ceruloplasmin oxidase activity was significantly decreased in WD patients (0.87 U/L, IQR 0.61-1.54). The optimal cut-off of serum ceruloplasmin oxidase activity to identified WD is 7 U/L, with sensitivity and specificity of 97.03 % and 98.19 %, respectively. Furthermore, this study revealed a positive correlation between enzymatic and immunoreactive serum ceruloplasmin tests. As primary diagnostic methods, serum ceruloplasmin levels below the diagnostic cut-offs for either the enzymatic or immunoreactive tests were observed in 818 out of 842 WD patients (97.15 %). Compared with the presence of K-F rings in asymptomatic patients, the accuracy of serum ceruloplasmin tests was significantly higher (56.12 % VS 95.08 %). Moreover, the positive rate of cranial MRI in neurological patients was similar to the tests of serum ceruloplasmin (92.91 % VS 97.40 %). Moreover, 71 patients had ambiguous genetic results, complicating the diagnosis. However, serum ceruloplasmin tests successfully identified 65 out of these 71 patients (91.55 %)., Conclusion: Serum ceruloplasmin oxidase activity has excellent performance in diagnosing WD, which should be widely used as preferred test in WD patients., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow., Materials and Methods: 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE., Results: We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (β = -11.755, P=0.001), LAA FV (β = -17.364, P=0.004), LAA PEV (β = -18.743, P<0.001), and LAA WMV (β = -7.740, P=0.001) in multiple linear regression analysis., Conclusions: LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Peripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac function based on cardiac self-repair is not well understood., Objectives: This study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS., Methods: The activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to evaluate the autonomic tone directly. The pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested., Results: Sympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS at acupoint PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS at acupoint ST36 had a limited effect. Both iPENS at PC6 and ST36 improved the autonomic and cardiac function of rats in the cPENS groups., Conclusion: Rats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation., Competing Interests: Disclosures The authors do not have any possible conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Fragile X syndrome is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus. Given the relatively low prevalence but large population, the distinct health care system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1 of 850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1 of 356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies-no screening, population-based screening, targeted screening, and our pilot screening-indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening because of their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Verticillium dahliae causes a serious decline in cotton yield and quality, posing a serious threat to the cotton industry. However, the mechanism of resistance to V. dahliae in cotton is still unclear, which limits the breeding of resistant cultivars., Methods: To analyze the defense mechanisms of cotton in response to V. dahliae infection, we compared the defense responses of two upland cotton cultivars from Xinjiang (JK1775, resistant; Z8,susceptible) using transcriptome sequencing at different infection stages., Results: The results revealed a significant differential expression of genes in the two cotton cultivars post V. dahliae infection, with the number of DEGs in JK1775 being higher than that in Z8 at different infection stages of V. dahliae . Interestingly, the DEGs of both JK1775 and Z8 were enriched in the MAPK signaling pathway in the early and late stages of infection. Importantly, the upregulated DEGs in both cultivars were significantly enriched in all stages of the phenylpropanoid metabolic pathway. Some of these DEGs were involved in the regulation of lignin and coumarin biosynthesis, which may be one of the key factors contributing to the resistance of upland cotton cultivars to V. dahliae in Xinjiang. Lignin staining experiments further showed that the lignin content increased in both resistant and susceptible varieties after inoculation with V. dahliae ., Discussion: This study not only provides insights into the molecular mechanisms of resistance to Verticillium wilt in Xinjiang upland cotton but also offers important candidate gene resources for molecular breeding of resistance to Verticillium wilt in cotton., 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 © 2024 Zhang, Ma, Wang, Gao, Zhao, Yu, Zhang and Xi.)

Ethnopharmacological Relevance: The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM., Purpose: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments., Methods: The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein-protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1β, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing., Results: Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS.In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]&#95;ruminantium&#95;group, Colidextribacter, Romboutsia, and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria., Conclusion: Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application., 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. Published by Elsevier B.V.)

Background: Cinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified., Purpose: Our study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary., Methods: The toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS., Results: Cin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12‑hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae&#95;NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed., Conclusion: As a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines., Competing Interests: Declaration of competing interest The authors (Na Han, Taotao Wang, Sheng Chang, Rong Gao, Yuanyuan Wen, Zhihui Liu, Haoying Xi, Jianxiu Zhai, Ruimao Feng, Sikai Li, Jun Yin) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All data were generated inhouse, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy., (Copyright © 2024. Published by Elsevier GmbH.)

Introduction: Tendon-derived stem cells (TDSCs) play a critical role in tendon repair. N5-methylcytosine (m5C) is a key regulator of cellular processes such as differentiation. This study aimed to investigate the impact of m5C on TDSC differentiation and the underlying mechanism., Methods: TDSCs were isolated from rats and identified, and a tendon injury rat model was generated. Tenogenic differentiation in vitro was evaluated using Sirius red staining and quantitative real-time polymerase chain reaction, while that in vivo was assessed using immunohistochemistry and hematoxylin‒eosin staining. m5C methylation was analyzed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability assay., Results: The results showed that m5C levels and NSUN2 expression were increased in TDSCs after tenogenic differentiation. Knockdown of NSUN2 inhibited m5C methylation of KLF2 and decreased its stability, which was recognized by YBX1. Moreover, interfering with KLF2 suppressed tenogenic differentiation of TDSCs, which could be abrogated by KLF2 overexpression. Additionally, TDSCs after NSUN2 overexpression contributed to ameliorating tendon injury in vivo . In conclusion, NSUN2 promotes tenogenic differentiation of TDSCs via m5C methylation of KLF2 and accelerates tendon repair., Conclusions: The findings suggest that overexpression of NSUN2 can stimulate the differentiation ability of TDSCs, which can be used in the treatment of tendinopathy., Competing Interests: 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., (© 2024 The Author(s).)

Staphylococcus aureus is a notorious pathogen predominantly involved in skin and soft tissue infections, exhibiting a distinct innate sex bias. This study explores the influence of testosterone on the virulence of S. aureus and elucidates its underlying mechanisms. Utilizing a skin abscess model in intact and castrated male mice, we assessed the effects of testosterone on S. aureus pathogenicity. Compared to controls, castrated mice showed significantly reduced abscess sizes and decreased bacterial loads, highlighting the role of testosterone in modulating the severity of S. aureus infections. In vitro experiments revealed that testosterone enhances the hemolytic activity, cytotoxicity, and oxidative stress resistance of S. aureus. Real-time quantitative PCR analysis showed a significant upregulation of the genes encoding α-hemolysin (hla) and phenol-soluble modulin (psmα). Importantly, testosterone treatment significantly enhanced the expression of the accessory gene regulator (Agr) quorum-sensing system components (agrC, agrA, agrB, agrD), while the SaeRS system (saeR, saeS, and sbi) exhibited only slight changes. Gene knockout experiments revealed that deletion of agrC, rather than saeRS and agrBD, abolishes the testosterone-induced enhancement of hemolysis and gene expression, underscoring the key role of AgrC. Molecular docking simulations indicated a direct interaction between testosterone and AgrC protein, with a strong binding affinity at the active site residue SER201. This study provides new insights into the mechanistic basis of how testosterone enhances the pathogenicity of S. aureus, potentially contributing to increased male susceptibility to S. aureus infections and offering a targeted approach for therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: An updated summary of the research profile of nutrition for the last 30 years for decompensated cirrhosis is lacking. This study aimed to explore the literature on nutrition for decompensated cirrhosis, draw a visual network map to investigate the research trends, and provide suggestions for future research. The Web of Science database retrieves the literature on nutrition for decompensated cirrhosis between 1994 and 2024., Methods: We used the cooperative, co-occurrence, and co-citation networks in the CiteSpace knowledge graph analysis tool to explore and visualize the relevant countries, institutions, authors, co-cited journals, keywords, and co-cited references., Results: We identified 741 articles on nutrition for decompensated cirrhosis. The number of publications and research interests has generally increased. The USA contributed the largest number of publications and had the highest centrality. The University of London ranked first in the number of articles issued, followed by the University of Alberta and Mayo Clinic. TANDON P, a "core strength" researcher, is a central hub in the collaborative network. Of the cited journals, HEPATOLOGY had the highest output (540, 15.3%)., Conclusions: Over the past three decades, the focus of research on nutrition in decompensated cirrhosis has shifted from "hepatic encephalopathy, intestinal failure, metabolic syndrome, and alcoholic hepatitis" to "sarcopenia and nutritional assessment." In the future, nutritional interventions for sarcopenia should be based on a multimodal approach to address various causative factors. Its targeted treatment is an emerging area that warrants further in-depth research.

Although antibody-based immune checkpoint blockades have been successfully used in antitumor immunotherapy, the low response rate is currently the main problem. In this work, a small-molecule programmed cell death-ligand (PD-L1) inhibitor, LG-12, was developed and radiolabeled with 131 I to obtain the chemically and biologically identical radiopharmaceutical [ 131 I]LG-12, which aimed to improve the antitumor effect by combination of LG-12 and [ 131 I]LG-12. LG-12 showed high inhibitory activity to PD-1/PD-L1 interaction. The results of cell uptake and biodistribution studies indicated that [ 131 I]LG-12 could specifically bind to PD-L1 in B16-F10 tumors. It could induce immunogenic cell death and the release of high mobility group box 1 and calreticulin. The combination of [ 131 I]LG-12 and LG-12 could significantly inhibit tumor growth and resulted in enhanced antitumor immune response. This PD-L1 small-molecule inhibitor based combination strategy has great potential for tumor treatment., 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 Inc. All rights reserved.)

Inguinal hernias are the most common type of enterocele and are frequently caused by defects in the abdominal wall muscles in the groin area. Numerous animal models and human studies have shown that the gut microbiota is associated with skeletal muscle aging and loss. However, the causation between the gut microbiota and inguinal hernia remains unclear. To reveal the causal association between the gut microbiota and inguinal hernia, we conducted a two-sample double-sided Mendelian randomization analysis. We used genome-wide association analysis (GWAS) summary statistics of the gut microbiota from the MiBioGen consortium and GWAS statistics of inguinal hernia from the FinnGen R10 database. The causation between the gut microbiota and inguinal hernia was explored through the inverse variance weighted (IVW) method, MR Egger regression method, weighted median method, weighted model method, and simple model method. Sensitivity analysis was used to test whether the Mendelian randomization analysis results were reliable. Reverse Mendelian randomization was used to conduct effect analysis and sensitivity analysis using the entire gut microbiota as the outcome. The IVW results indicated that Verrucomicrobia, Lactobacilliales, Clostridiaceae1, Butyricococcus, Categorybacter, Hungatella, Odoribacter, and Olsenella had a direct negative causation with the gut microbiota. The reverse Mendelian Randomization results showed that Eubacterium brachygroup, Eubacterium eligensgroup, Eubacterium xylanophilumgroup, Coprococcus3, Ruminococcus1, and Senegalimassilia were directly related to inguinal hernia. The bilateral sensitivity analysis revealed no heterogeneity or horizontal pleiotropy. The results confirmed that 8 bacterial traits had a negative causation with inguinal hernia. Reverse MR analysis revealed a positive correlation between inguinal hernia and 6 bacterial traits. Modulating the diversity and components of the gut microbiota is envisaged to contribute to improving the incidence and prognosis of inguinal hernia., (© 2024. The Author(s).)

Rationale and Objectives: The pericoronary fat attenuation index (FAI) values around plaques may reveal the relationship between periplaque vascular inflammation and different plaque component volume fractions. We aimed to evaluate the potential associations between periplaque FAI values and plaque component volume fractions., Materials and Methods: 496 patients (1078 lesions) with coronary artery disease, who underwent computed tomography angiography (CCTA) between September 2022 and August 2023, were analyzed retrospectively. Each lesion was characterized and the plaque component volume fractions and periplaque FAI values were measured. Multiple linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (Qgcomp) were used to explore the relationship between plaque component volume fractions and the risk of elevated periplaque FAI values., Results: After adjusting for clinical characteristics, multiple linear regression identified that lipid components volume fraction (β = 0.162, P < 0.001) were independent risk factors for elevated periplaque FAI values whereas calcified components volume fraction (β = -0.066, P = 0.025) were independent protective factors. The WQS regression models indicated an increase in the overall confounding effect of the adjusted lipid indices and plaque composition volume fraction on the risk of elevated periplaque FAI values (P = 0.004). Qgcomp analysis indicated lipid component volume fraction and calcified component volume fraction was positively and negatively correlated with elevated plaque FAI values, respectively (all P < 0.05)., Conclusions: Periplaque FAI values quantified by CCTA were strongly correlated with lipid and calcification component volume fractions., 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.)

Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering legumain is overexpressed in multiple types of human cancers, a 131 I-labeled radiopharmaceutical ([ 131 I]MAAN) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) was developed by us recently for treating legumain-overexpressed tumors. However, liver enrichment limits its application. In this study, a new radiopharmaceutical [ 131 I]IM(HE) 3 AAN was designed and synthesized by introducing a hydrophilic peptide sequence His-Glu-His-Glu-His-Glu ((HE) 3 ) into [ 131 I]MAAN to optimize the pharmacokinetics. Upon activation by legumain under a reducing environment, hydrophilic [ 131 I]IM(HE) 3 AAN could react with its precursor to form heterologous dimer [ 131 I]H-Dimer that is highly hydrophobic. Cerenkov imaging revealed that [ 131 I]IM(HE) 3 AAN displayed superior tumor selectivity and longer tumor retention time as compared with [ 131 I]MAAN, with a significant reduction in the liver uptake. After an 18-day treatment with [ 131 I]IM(HE) 3 AAN, the tumor proliferation was obviously inhibited, while no obvious injury was observed in the normal organs. These findings suggest that [ 131 I]IM(HE) 3 AAN could serve as a promising drug candidate for treating legumain-overexpressed tumors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The escalating rates of melanoma and non-melanoma skin cancers highlight the urgent need for enhanced diagnostic tools. This study evaluates the effect of hair presence in dermoscopic images on AI-driven skin lesion recognition, using 10,015 images from the HAM10000 collection. Images were categorized based on the extent of hair occlusions to assess their impact on AI performance. Advanced metrics like Gradient-weighted Class Activation Mapping and novel infection metrics provided deeper insights into the model's focus and segmentation efficacy. The results revealed that the AI model achieved an impressive overall accuracy of 95.3 % and an Area Under the Curve (AUC) of 99.1 %, maintaining high performance across various lesion types. Performance varied with hair occlusion levels; it was optimal under few hair occlusions but dropped significantly when hair was abundant. For instance, Vascular Lesions saw a dramatic decrease in performance metrics from 0.515 to 0.115 under heavy hair occlusion, while Actinic Keratoses and Intraepithelial Carcinoma were least affected. Sparse hair occasionally improved accuracy, suggesting its potential utility in training robust models. The study underscores the complex impact of hair on AI diagnostics in dermatology, advocating for the development of advanced preprocessing techniques and hair-robust algorithms to enhance AI diagnostic capabilities., 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.)

Terrestrial ecosystems are critical to the global carbon cycle and climate change mitigation. Over the past two decades, the Yangtze River Basin (YRB) has implemented various ecological restoration projects and active management measures, significantly impacting carbon stock patterns. This study employed random forest models to analyze the spatial and temporal patterns of carbon stocks in the YRB from 2001 to 2021. In 2021, carbon density in the YRB ranged from 8.5 to 177.4 MgC/ha, with a total carbon stock of 18.05 PgC. Over 20 years, the YRB sequestered 1.26 billion tons of carbon, accounting for 11.28 % of the region's fossil fuel carbon emissions. Notably, forests exhibited the highest carbon density, averaging 98.01 ± 25.01 MgC/ha (2021) with a carbon stock growth rate of 51.6 TgC/yr. Piecewise structural equation model was used to assess the effects of climate and human activities on carbon density, revealing regional variability, with unique patterns observed in the source region. Human activities primarily influence carbon density indirectly through vegetation alterations., while climate change directly impacts ecosystem biophysical processes. These findings offer critical insights for climate mitigation and adaptation strategies, enhancing the understanding of carbon dynamics for sustainable development and global carbon management., 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 B.V. All rights reserved.)

Background: Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored., Methods: In this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism., Results: Our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition., Conclusion: In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future., 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 © 2024 Wu, Wang, Tan, Ran, Guan, Qian, Feng, Jiang, Peng, Sheng, Xi, Ji and Guo.)

Background: The factors influencing vaccination decision-making for newly developed vaccines may be similar to and different from those for established vaccines. Understanding these underlying differences and similarities is crucial for designing targeted measures to promote new vaccines against potential novel viruses., Objective: This study aims to compare public vaccination decisions for newly developed and established vaccines and to identify the differences and similarities in the influencing factors., Method: A discrete choice experiment (DCE) was conducted on 1,509 representatives of the general population in China to collect data on preferences for the coronavirus disease 2019 (COVID-19) and influenza vaccines, representing the newly developed and established vaccines, respectively. The latent class logit model was used to identify latent classes within the sample, allowing for an analysis of the factors distinctly influencing choices for both types of vaccines., Result: Participants valued similar attributes for both vaccines. However, concerns about sequelae were more significant for the newly developed vaccine, while effectiveness was prioritized for the established vaccine. Class membership analysis revealed these differences and similarities were significantly correlated with age, health, yearly household income, acquaintances' vaccination status, and risk perception., Conclusion: The study highlights the need for tailored communication strategies and targeted vaccination interventions. For the newly developed vaccines, addressing concerns about side effects is more crucial. For long-standing vaccines, emphasizing their effectiveness can enhance uptake more significantly. Engaging healthcare providers and community influencers is essential for both vaccines to increase public confidence and vaccination rates. Clear communication and community engagement are critical strategies for addressing public concerns and misinformation, particularly during periods of heightened concern., 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 © 2024 Chang, Xu, Xi and Shao.)

Background: Assisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured., Purpose: This study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis., Methods: We compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women., Results: Our study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance., Conclusions: This study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health., (© 2024. The Author(s).)

Background: Reproductive aging can adversely affect male fertility and the health of offspring. The aging process is accompanied by impaired autophagy. Recent studies have shown that Trehalose plays an important role in the prevention of various diseases by regulating autophagy. However, the roles of Trehalose in testicular aging and reproductive decline remain to be clarified., Objective: The present study aimed to evaluate the protective effects of Trehalose on testes in an aging mouse model., Materials and Methods: In this study, an in vivo aging model in mice by administering D-galactose was established to explore the protective effect of Trehalose on testicular aging. We examined histological changes and related indicators of apoptosis, autophagy, mitochondrial biogenesis, and sperm quality., Results: D-galactose treatment induced oxidative stress, apoptosis, and impairment of autophagy of testicular cells in mouse testes. Trehalose administration significantly reduced germ cell apoptosis and DNA damage caused by D-galactose-induced oxidative stress. Notably, Trehalose activated autophagy activity and improved mitochondrial function in testicular cells. Furthermore, Trehalose treatment increased the expression level of the tight junction protein ZO-1, and accelerated clearance of damaged mitochondria in Sertoli cells, indicating that Trehalose ameliorated Sertoli cell function in D-galactose-induced aging testes., Discussion and Conclusion: These findings suggest that Trehalose administration activated the autophagy activity in testicular cells and improved mitochondrial function, thereby effectively preventing testicular aging. Trehalose and its activated autophagy are crucial for preventing testicular aging, thus restoring autophagy activity by administering Trehalose could be a promising means to delay aging., (© 2024 American Society of Andrology and European Academy of Andrology.)

Porous poly (lactic-co-glycolic acid)/ β -tricalcium phosphate/Icaritin (PLGA/ β -TCP/ICT, PTI) scaffold is a tissue engineering scaffold based on PLGA/ β -TCP (PT) containing Icaritin, the main active ingredient of the Chinese medicine Epimedium. Due to its excellent mechanical properties and osteogenic effect, PTI scaffold has the potential to promote bone defect repair. However, the release of ICT from the scaffolds is difficult to control. In this study, we constructed Ti 3 C 2 T x @PLGA/ICT microspheres (TIM) and evaluated their characterization as well as ICT release under near-infrared (NIR) irradiation. We utilized TIM to modify the PT scaffold and performed biological experiments. First, we cultured rat bone marrow mesenchymal stem cells on the scaffold to assess biocompatibility and osteogenic potential under on-demand NIR irradiation. Subsequently, to evaluate the osteogenic properties of TIM-modified scaffold in vivo , the scaffold was implanted into a femoral condyle defect model. TIM have excellent drug-loading capacity and encapsulation efficiency for ICT, and the incorporation of Ti 3 C 2 T x endows TIM with photothermal conversion capability. Under 0.90 W cm -2 NIR irradiation, the temperature of TIM maintained at 42.0 ± 0.5 °C and the release of ICT was accelerated. Furthermore, while retaining its original properties, the TIM-modified scaffold was biocompatible and could promote cell proliferation, osteogenic differentiation, and biomineralization in vitro , as well as the osteogenesis and osseointegration in vivo , and its effect was further enhanced through the modulation of ICT release under NIR irradiation. In summary, TIM-modified scaffold has the potential to be applied in bone defects repairing., (Creative Commons Attribution license.)

Aerococcus viridans ( A. viridans ) is an important opportunistic zoonotic pathogen that poses a potential threat to the animal husbandry industry, such as cow mastitis, due to the widespread development of multidrug-resistant strains. Phage lysins have emerged as a promising alternative antibiotic treatment strategy. However, no lysins have been reported to treat A. viridans infections. In this study, the critical active domain and key active sites of the first A. viridans phage lysin AVPL were revealed. AVPL consists of an N-terminal N-acetylmuramoyl-L-alanine amidase catalytic domain and a C-terminal binding domain comprising two conserved LysM. H40, N44, E52, W68, H147, T157, F60, F64, I77, N92, Q97, H159, V160, D161, and S42 were identified as key sites for maintaining the activity of the catalytic domain. The LysM motif plays a crucial role in binding AVPL to bacterial cell wall peptidoglycan. AVPL maintains stable activity in the temperature range of 4-45°C and pH range of 4-10, and its activity is independent of the presence of metal ions. In vitro, the bactericidal effect of AVPL showed efficient bactericidal activity in milk samples, with 2 µg/mL of AVPL reducing A. viridans by approximately 2 Log 10 in 1 h. Furthermore, a single dose (25 µg) of lysin AVPL significantly reduces bacterial load (approximately 2 Log 10) in the mammary gland of mice, improves mastitis pathology, and reduces the concentration of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in mammary tissue. Overall, this work provides a novel alternative therapeutic drug for mastitis induced by multidrug-resistant A. viridans ., Importance: A. viridans is a zoonotic pathogen known to cause various diseases, including mastitis in dairy cows. In recent years, there has been an increase in antibiotic-resistant or multidrug-resistant strains of this pathogen. Phage lysins are an effective approach to treating infections caused by multidrug-resistant strains. This study revealed the biological properties and key active sites of the first A. viridans phage lysin named AVPL. AVPL can effectively kill multidrug-resistant A. viridans in pasteurized whole milk. Importantly, 25 μg AVPL significantly alleviates the symptoms of mouse mastitis induced by A. viridans . Overall, our results demonstrate the potential of lysin AVPL as an antimicrobial agent for the treatment of mastitis caused by A. viridans ., Competing Interests: The authors declare no conflict of interest.

Uterine fibroids are common benign tumors originating from the uterus's smooth muscle layer, often leading to symptoms such as pelvic pain, and reproductive issues. Early detection is crucial to prevent complications such as infertility or the need for invasive treatments like hysterectomy. One of the main challenges in diagnosing uterine fibroids is the lack of specific symptoms, which can mimic other gynecological conditions. This often leads to under-diagnosis or misdiagnosis, delaying appropriate management. In this research, an attention based fine-tuned EfficientNetB0 model is proposed for the classification of uterine fibroids from ultrasound images. Attention mechanisms, permit the model to focus on particular parts of an image and move forward the model's execution by empowering it to specifically go to imperative highlights whereas overlooking irrelevant ones. The proposed approach has used a total of 1990 images divided into two classes: Non-uterine fibroid and uterine fibroid. The data augmentation methods have been connected to improve generalization and strength by exposing it to a wider range of varieties within the training data. The proposed model has obtained the value of accuracy as 0.99. Future research should focus on improving the accuracy and efficiency of diagnostic techniques, as well as evaluating their effectiveness in diverse populations with higher sensitivity and specificity for the detection of uterine fibroids, as well as biomarkers to aid in diagnosis., (© 2024. The Author(s).)

Hypertrophic scar (HS) is a fibrous proliferative disorder that occurs in the dermis after skin injury. Studies have confirmed that Botulinum toxin type A (BTA) is effective in scar prevention and treatment. However, the specific mechanism remains uncertain. Hypertrophic scar fibroblasts (HSFs) and normal skin fibroblasts (NSFs) from the skin tissues of HS patients were isolated and cultured. Western blot analysis was conducted to measure the expression of JAK2/STAT3 pathway-related proteins. HSFs were treated with the JAK2 inhibitor (AG490) or agonist (C-A1). The CCK-8 assay, EdU staining, scratch-wound assay and transwell assay were used to examine the biological properties of HSFs. Western blot, immunofluorescence, and Sirius red staining were used to assess the fibrosis of HSFs. Additionally, a mouse full-thickness wound model was constructed to investigate the role of BTA in wound healing. The results showed that the JAK2 and STAT3 phosphorylation levels were markedly increased in HS tissues and HSFs. AG490 treatment reduced cell viability, proliferation and migration capacity, and inhibited the fibrosis of HSFs, whereas C-A1 treatment had the opposite effect. BTA treatment inhibited the JAK2/STAT3 pathway. BTA reduced cell viability, proliferation and migration ability, and inhibited the fibrosis of HSFs, while C-A1 intervention weakened the impact of BTA. Meanwhile, BTA promoted wound healing and reduced collagen deposition in vivo. In conclusion, BTA inhibited the JAK2/STAT3 pathway, which in turn hindered the proliferation, migration and fibrosis of HSFs, and promoted wound healing in mice.

Solar-driven methanation of carbon dioxide (CO 2 ) with water (H 2 O) has emerged as an important strategy for achieving both carbon neutrality and fuel production. The selective methanation of CO 2 was often hindered by the sluggish kinetics and the multiple competition of other C 1 byproducts. To overcome this bottleneck, we utilized a biomass synthesis method to synthesize SiC rods and then constructed a direct Z-scheme heterojunction Co 3 O 4 /SiC catalyst. The substantial difference in work functions between SiC and Co 3 O 4 served as a significant source of the charge driving force, facilitating the conversion of CO 2 to CH 4 . The high-valent cobalt Co(IV) in Co 3 O 4 acts as an active species to promote efficient dissociation of water. This favorable condition greatly enhanced the likelihood of a high concentration of electrons and protons around a single site on the catalyst surface for CO 2 methanation. DFT calculation showed that the energy barrier of CO 2 hydrogenation was significantly reduced at the Co 3 O 4 /SiC heterojunction interface, which changed the reaction pathway and completely converted the product from CO to CH 4 . The optimum CH 4 evolution rate of Co 3 O 4 /SiC samples was 21.3 μmol g -1 h -1 with 100% selectivity. This study has an important guiding significance for the selective regulation of CO 2 to CH 4 products in photocatalysis applications.

Objective: This study aimed to investigate the correlation between serum 25-hydroxyvitamin D (25(OH)D) levels and retinopathy of prematurity (ROP) in premature infants one month after birth., Methods: Preterm infants (gestational age <32 weeks) admitted to the Affiliated Hospital of Qingdao University from 2017 to 2022 were divided into ROP and non-ROP groups based on ROP occurrence any stage. Serum 25(OH)D levels and clinical data were compared between the two groups at 1 month after birth, and the relationship between vitamin D levels and ROP was analyzed., Results: Among the 217 premature infants included, 55 (25.35%) were in the ROP group, and 162 (74.65%) were in the non-ROP group. The ROP group had lower gestational age and birth weight, longer invasive ventilation (IV), non-invasive ventilation (NIV), and oxygen therapy times compared to the non-ROP group. Apgar scores, cesarean delivery, and antenatal steroids ratios were lower in the ROP group, while sepsis and pulmonary surfactant utilization ratios were higher (all p  < 0.05). Significant differences in serum 25-(OH)D levels were observed among children in the non-ROP group (14.20 ± 5.07 ng/ml), ROP treated group (7.891 ± 1.878 ng/ml), and untreated group (12.168 ± 4.354 ng/ml) ( p  < 0.001). Multivariate regression analysis identified antenatal steroids as protective factors and lower birth weight, serum 25-(OH)D levels, long-term invasive mechanical ventilation, and sepsis as independent risk factors for ROP in premature infants., Conclusion: Vitamin D, lower birth weight, long-term invasive mechanical ventilation, and sepsis were associated with incidence of ROP in preterm infants. Vitamin D was associated with the severity of ROP, emphasizing the importance of prudent vitamin D supplementation and regular monitoring of serum 25-(OH)D levels., 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., (© 2024 Yin, Xu, Zhang, Li, Xi, Ma, Sun, Yang, Li and Jiang.)

The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of PCOS by targeting autophagy. Relevant literatures were searched in the following databases, including: PubMed, MEDLINE, Web of Science, Scopus. The search terms were "autophagy", "PCOS", "polycystic ovary syndrome", "ovulation", "hyperandrogenemia", "insulin resistance", "inflammatory state", "circadian rhythm" and "treatment", which were combined according to the retrieval methods of different databases. Through analysis, we uncovered that abnormal levels of autophagy were closely related to abnormal ovulation, insulin resistance, hyperandrogenemia, and low-grade inflammation in patients with PCOS. Lifestyle intervention, melatonin, vitamin D, and probiotics, etc. were able to improve the pathological mechanism of PCOS via targeting autophagy. In conclusion, autophagy disorder is a key pathological mechanism in PCOS and is also a potential target for drug development and design., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Legionella is an opportunistic waterborne pathogen that causes Legionnaires' disease. It poses a significant public health risk, especially to vulnerable populations in health care facilities. It is ubiquitous in manufactured water systems and is transmitted via inhalation or aspiration of aerosols/water droplets generated from water fixtures (e.g., showers and hand basins). As such, the effective management of premise plumbing systems (building water systems) in health care facilities is essential for reducing the risk of Legionnaires' disease. Chemical disinfection is a commonly used control method and chlorine-based disinfectants, including chlorine, chloramine, and chlorine dioxide, have been used for over a century. However, the effectiveness of these disinfectants in premise plumbing systems is affected by various interconnected factors that can make it challenging to maintain effective disinfection. This systematic literature review identifies all studies that have examined the factors impacting the efficacy and decay of chlorine-based disinfectant within premise plumbing systems. A total of 117 field and laboratory-based studies were identified and included in this review. A total of 20 studies directly compared the effectiveness of the different chlorine-based disinfectants. The findings from these studies ranked the typical effectiveness as follows: chloramine > chlorine dioxide > chlorine. A total of 26 factors were identified across 117 studies as influencing the efficacy and decay of disinfectants in premise plumbing systems. These factors were sorted into categories of operational factors that are changed by the operation of water devices and fixtures (such as stagnation, temperature, water velocity), evolving factors which are changed in-directly (such as disinfectant concentration, Legionella disinfectant resistance, Legionella growth, season, biofilm and microbe, protozoa, nitrification, total organic carbon(TOC), pH, dissolved oxygen(DO), hardness, ammonia, and sediment and pipe deposit) and stable factors that are not often changed(such as disinfectant type, pipe material, pipe size, pipe age, water recirculating, softener, corrosion inhibitor, automatic sensor tap, building floor, and construction activity). A factor-effect map of each of these factors and whether they have a positive or negative association with disinfection efficacy against Legionella in premise plumbing systems is presented. It was also found that evaluating the effectiveness of chlorine disinfection as a water risk management strategy is further complicated by varying disinfection resistance of Legionella species and the form of Legionella (culturable/viable but non culturable, free living/biofilm associated, intracellular replication within amoeba hosts). Future research is needed that utilises sensors and other approaches to measure these key factors (such as pH, temperature, stagnation, water age and disinfection residual) in real time throughout premise plumbing systems. This information will support the development of improved models to predict disinfection within premise plumbing systems. The findings from this study will inform the use of chlorine-based disinfection within premise plumbing systems to reduce the risk of Legionnaires disease., Competing Interests: Declaration of competing interest Hao Xi and Jason Hinds work for Enware Pty Ltd, Caringbah, NSW, Australia, a manufacturer of specialist plumbing and safety products. All other 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)