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Abstract Background Metabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear. Aim of the study This study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism. Methods High-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment. Results ZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver. Conclusion Our study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY.

Abstract Background The impact of the etiology of rotator cuff injury (RCI) on outcomes after rotator cuff repair remains unclear. This study aimed to evaluate the postoperative outcomes of patients with RCIs of different etiologies and identify the risk factors affecting prognosis. Methods This study included 73 patients with RCI who underwent arthroscopic rotator cuff repair. The patients were categorized into either a traumatic group or a non-traumatic group based on their history of trauma. Preoperative and postoperative assessments included shoulder range of motion, muscle strength, and physical examination findings specific to the shoulder for both groups. Clinical differences between arthroscopic repair of traumatic and non-traumatic RCIs were evaluated using univariate analysis. Logistic regression analysis determined independent risk factors for rotator cuff repair prognosis. Results Among the 73 patients, 31 were in the traumatic group and 42 in the non-traumatic group, with a minimum postoperative follow-up of 12 months and a mean follow-up of 13.8 months. The duration of the disease was significantly longer in the non-traumatic group compared with the traumatic group (P

Abstract Background Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities. Results Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male’s. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences. Conclusions In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.

Abstract Two-dimensional (2D) multiferroic materials are recognized as promising candidates for next-generation nanodevices due to their tunable magnetoelectric coupling and distinctive physical phenomena. In this study, we proposed a novel 2D multiferroic van der Waals heterostructure (vdWH) by stacking atomic layers of ferroelectric In2Se3 and ferromagnetic MnI3. Using first-principles calculations, we found that the MnI3/In2Se3 vdWH exhibit robust metallic conductivity across various spin and polarization states, preserving the distinctive band characteristics of isolated In2Se3 and MnI3. However, the alignment of Fermi levels causes the conduction band minimum (CBM) and valence band maximum (VBM) of In2Se3 and MnI3 to shift relative to their original band structures. Remarkably, the MnI3/In2Se3 with the upward polarization state of In2Se3 exhibits an Ohmic contact. Switching the polarization direction of In2Se3 from upward to downward can transform the MnI3/In2Se3 vdWH from an Ohmic contact to a p-type Schottky contact, while also modifying its dipole moment, magnetic strength and direction. Based on these properties of MnI3/In2Se3 vdWH, we designed the field-effect transistors (FETs) with high on/off rates and nonvolatile data storage device. Furthermore, the Schottky barrier heights (SBHs), magnetic moment, and dipole moment of MnI3/In2Se3 vdWH can also be effectively regulated by reducing the interlayer distance. With the continuous reduction of the interlayer distance of MnI3/In2Se3 vdWH, its easy magnetization axis is expected to shift from in-plane to out-of-plane. These findings offer new insights for the design and development of the next-generation spintronic and nonvolatile memory nanodevices.

To explore the quality characteristics of fermented passion fruit wine, this study used high performance liquid chromatography, gas chromatography-mass spectrometry (GC-MS), electronic nose technology and sensory evaluation methods to determine its organic acid content, amino acid content, volatile substances and sensory properties. The results showed that passion fruit wine had the highest citric acid content and a total free amino acid content of 22.08 mg/100 g after alcoholic fermentation. The color intensity of the samples was significantly (P1) were ethyl butyrate, phenethyl alcohol and ethyl caproate. In summary, the flavor of passion fruit wine fermented by yeast was quite different from that of the original fruit juice, and the aroma of fruit wine was richer.

Abstract Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination.

The aim of the study was to compare the efficacy of Mathieu combined urethral plate incision (Mathieu-IP) versus onlay island flap urethroplasty in patients with distal hypospadias complicated by urethral stenosis. The clinical data of 70 patients with distal hypospadias complicated by urethral plate stenosis treated in the Department of Urology, Anhui Provincial Children’s Hospital (Hefei, China), from May 2019 to May 2022, were retrospectively analyzed. Thirty-eight patients underwent Mathieu-IP (Mathieu-IP group) and 32 underwent onlay island flap urethroplasty (Onlay group). Follow-ups at 1 month, 6 months, and 12 months postoperatively assessed operative time, complications, urethral meatus morphology, and family satisfaction. The Mathieu-IP group had significantly shorter operative time (mean ± standard deviation [s.d.]: 81.58 ± 5.18 min) versus the Onlay group (mean ± s.d.: 110.75 ± 6.05 min; P < 0.05). Surgical success rates were 78.9% (Mathieu-IP group) and 75.0% (Onlay group), with no significant difference (P > 0.05). Complications were comparable between the groups. The Mathieu-IP group resulted in a vertical slit-shaped urethral meatus in 89.5% versus 13.8% in the Onlay group (P < 0.05). Family satisfaction with general penile appearance and skin shape showed no significant differences, but the Mathieu-IP group had higher satisfaction with meatal position (P < 0.05). Mathieu-IP offers simplicity, safety, and shorter operative time compared to Onlay. Both the techniques effectively treat urethral plate stenosis in distal hypospadias, with reduced postoperative complications compared to tubularized incised plate urethroplasty. Mathieu-IP results in a vertical slit-shaped urethral meatus which enhances urinary stream, indicating its potential for broader adoption.

Abstract Background Secretory carrier membrane proteins (SCAMPs) form a family of integral membrane proteins and play a crucial role in mediating exocytosis in both animals and plants. While SCAMP genes have been studied in several plant species, their functions in cotton, particularly in response to abiotic stress, have not yet been reported. Results In this study, a total of 53 SCAMP genes were identified in G. arboreum, G. raimondii, G. hirsutum, and G. barbadense. These genes were classified into five groups based on a phylogenetic analysis with SCAMPs from Arabidopsis thaliana. The main factor driving the expansion of the SCAMP gene family in G. hirsutum is tandem and segmental duplication events. Using MEME, in addition to the conserved SCAMP domain, we identified 3–13 other domains in each GhSCAMP. The cis-element analysis suggested that GhSCAMPs were widely involved in cotton growth and development, and responses to abiotic stresses. RNA sequencing (RNA-Seq) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results showed that most GhSCAMPs were expressed highly in many tissues and had differential expression responses to drought, cold, and heat stresses. Knock-down of GhSCAMP2 and GhSCAMP4 by virus-induced gene silencing (VIGS) lead to a salt-sensitive phenotype and had a lower content of CAT, POD, and SOD. Conclusions This study identified SCAMP genes in four cotton species, enhancing our understanding of the potential biological functions of SCAMPs. Additionally, we demonstrated that GhSCAMP2 and GhSCAMP4 positively regulate cotton tolerance to salt stress.

Abstract Da Vinci robot-assisted pancreaticoduodenectomy offers advantages, including minimal invasiveness, precise, and safe procedures. This study aimed to investigate the clinical effectiveness of implementing enhanced recovery after surgery (ERAS) concepts in Da Vinci robot-assisted pancreaticoduodenectomy. A retrospective analysis was conducted on clinical data from 62 patients who underwent Da Vinci robot-assisted pancreaticoduodenectomy between January 2018 and December 2022. Among these patients, 30 were managed with ERAS principles, while 32 were managed using traditional perioperative management protocols. Surgical time, intraoperative blood loss, postoperative oral intake time, time to return of bowel function, time to ambulation, visual analog scale (VAS) pain scores, fluid replacement volume, length of hospital stay, total hospital expenses, complications, and patient satisfaction were recorded and compared between the two groups. Postoperative follow-up included assessment of postoperative functional scores, reoperation rates, SF-36 quality of life scores, and survival rates. The average follow-up time was 35.6 months (range: 12–56 months). There were no statistically significant differences in general characteristics, including age, surgical time, intraoperative blood loss, and preoperative medical history between the two groups (P > 0.05). Compared to the control group, the intervention group had an earlier postoperative oral intake time, faster return of bowel function, rapid ambulation, and shorter hospital stays (P 0.05). Implementing ERAS principles in Da Vinci robot-assisted pancreaticoduodenectomy substantially expedited postoperative recovery, lowered pain scores, and diminished complications. However, there were no notable differences in long-term outcomes between the two groups.

Abstract Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

[Introduction] The main shafting structure with double supports of single row tapered roller bearings has been widely used in wind turbines, and determining the appropriate bearing operating clearance is crucial for the reliable operation of bearings and the main shafting.[Method] A dynamics analysis model was established focusing on the main shafting of a medium speed permanent magnet wind turbine, incorporating the hub, main shaft, and both upwind and downwind bearing. The variation trends of bearing raceway life, load area, and maximum contact stress under different axial clearances were calculated. [Result] The ideal axial operating clearance range of matched single row tapered roller bearings has been identified as −0.74 ~ −0.3 mm. [Conclusion] The research results have significant implications for the reliable operation of bearings and main shafting, providing a method and reference for determining the axial operating clearance of matched single row tapered roller bearings.

With the continuous progress of China’s rural revitalization and the increasing aging population in coastal rural areas, it has become a research focus to make the indoor thermal environment more suitable for the elderly, especially in winter. This study took Qingdao’s coastal rural areas in the cold region of China as an example. A field survey was conducted in 110 coastal rural dwellings, and four typical dwellings were selected for on-site measurements. This study collected information on the characteristics of local residential buildings, the primary living spaces for the elderly, heating methods, and thermal satisfaction. It also documented the energy expenditure and thermal conditions of the surveyed dwellings. The research findings indicate that the current heating system, while capable of partially improving the indoor thermal environment, is still affected by poor thermal insulation performance. As a result, there are issues such as low average indoor temperature, significant temperature fluctuations, and overall thermal instability. The findings of this study provide comprehensive information on the heating modes used in coastal rural dwellings, and the results can be utilized to evaluate and further improve the thermal environment of dwellings in cold coastal rural areas.

Abstract Objectives To establish superb microvascular imaging (SMI) based thyroid imaging reporting and data system (SMI TI-RADS) for risk stratification of malignancy in thyroid nodules. Methods In total, 471 patients, comprising 643 thyroid nodules, who received conventional ultrasound (US), SMI, and a final diagnosis were extensively analyzed. A qualitative assessment of US features of the nodules was performed followed by univariable and multivariable logistic regression analyses, leading to the construction of the SMI TI-RADS, which was further verified using internal and external validation cohorts. Results Among the stand-alone US, predictive factors were the shape and margins of the nodules, echogenicity and echogenic foci, vascularity, extrathyroidal extension, ring-SMI patterns, penetrating vascularity, flow-signal enlarged, and vascularity area ratio. SMI TI-RADS depicted an enhanced area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.92, 0.96; p

Highlights Nonflammable gel polymer electrolyte (SGPE) is developed by in situ polymerizing trifluoroethyl methacrylate (TFMA) monomers with flame-retardant triethyl phosphate (TEP) solvents and LiTFSI–LiDFOB dual lithium salts. Molecular polarity interaction between TEP and PTFMA mitigates interfacial reactions and changes the solvation of Li+. SGPE forms stable inorganic-rich solid electrolyte interface/cathode electrolyte interface layer, exhibiting well compatibility with Li anode and LiCoO2-type high-voltage cathode.

The treatment of bone defects has always been a difficult problem in orthopedic clinical practice, and research on new materials is currently a hot topic. In this study, the biological safety and bone induction ability of a new magnesium-based amorphous alloy (Mg66Zn30Ca3Sr1) and zinc–magnesium powder were verified and compared in animal experiments. Thirty Sprague–Dawley rats were randomly divided into three groups, and a bone defect was made in the lateral condyle of the femur of the left hind limb. The blank group closed the wound after establishing the bone defect model, the control group added zinc–magnesium powder and chondroitin sulfate gel, and the experimental group added magnesium–zinc–calcium–strontium alloy and chondroitin sulfate gel with the same volume. Peripheral venous blood of rats was collected at 4, 8, and 12 weeks postoperatively, and alanine aminotransferase (ALT), aspartate transferase, creatinine, blood urea nitrogen, magnesium ion, and zinc ion levels were evaluated. The expression levels of bone morphogenetic protein 2 (BMP-2), osteoprotegerin (OPG), osteopontin (OPN), core binding factor α1 (RUNX2), and alkaline phosphatase (ALP) were detected using enzyme-linked immunosorbent assay (ELISA). After the rats were euthanized, samples were taken. X-rays and micro-computed tomography (CT) images of the bone defect were obtained, and hematoxylin and eosin and Masson staining were performed. This study shows that amorphous magnesium–zinc–calcium–strontium alloy is a biodegradable metal with good biocompatibility and bone induction and has good application prospects in treating bone defects.

Abstract Pomacea canaliculata is one of the most successful invader in worldwide, adversely affecting native ecosystem through direct predation or indirect competition, while the mechanism of indirect effects on native species remain poorly understood. To clarify the effects of P. canaliculata on the native near-niche species, Bellamya purificata, a widespread freshwater gastropod in China, was selected as the research subject. The changes of mortality, histology, antioxidant system as well as the intestinal flora diversity of B. purificata were explored in present study. The results showed that the median lethal dose of P. canaliculata culture solution for B. purificata was 23.76 ind/L and a concentration-dependent damage of both the gonad and hepatopancreas were observed, the gonadal villi were dissolved and the hepatopancreas cells were broken at 20 ind/L. Furthermore, different concentrations of P. canaliculata culture solution leading to the antioxidant damage on the enzyme or non-enzyme systems of B. purificata at various degrees. Additionally, a decrease in the diversity of the intestinal flora was observed, accompanied by an increase in the abundance of pathogenic bacteria such as Pseudomonas and Aeromonas after the exposure of the culture solution of P. canaliculata. Last, after being recovered in freshwater for 24 h, the antioxidant damage of B. purificata and the disturbance of intestinal flora diversity were still not recovered especially in the high concentration group. The indirect competitive mechanism of P. canaliculata culture solution on B. purificata were explored from the aspects of tissue, biochemical level and intestinal flora, which enriched the research of P. canaliculata invasion on native snails in China, and provided new insights for the study of the invasion strategy of P. canaliculata.

Abstract Three-dimensional (3-D) stereo images can be generated via computer-based image processing of CORONA stereo pairs. To a certain extent, important terrain and surface feature data extracted from these stereo images can improve the survey of archaeological sites and the identification and mapping of major landscapes. In this study, we focused on the identification of the archaeological ruins of Liangzhu City. An optical stereo model (red/blue stereo image) of the Liangzhu site was created through computer-based mosaicking and processing of CORONA remote-sensing stereo pairs taken in the 1960s and 1970s. By importing the optical stereo model into mobile phones, tablet computers, and other mobile devices, the research team undertook real-time locating of ruins via human observation, on-site investigation, and image overlay during a field survey and identified several Liangzhu-period dams, some of which have been confirmed via archaeological field investigations. The research team later applied the same method to the identification of tombs at the site of the mausoleums of the six emperors of the Southern Song dynasty. The results further prove that this method is feasible and reliable and can be widely promoted and used for the identification of archaeological ruins.

Abstract The direct synthesis of light aromatics, especially para-xylene (p-X), from syngas/CO2 is drawing strong interest, but improving the space-time yield (STY) of p-X is a significant challenge. Here, a dynamic “dual-engine-driven” (DED) catalytic system is designed by combining two partners of ZnCr and FeMn (named “dual-engine”) with Z5@SiO2 capsule zeolite. The DED catalyst of 1.0%FeMn&[ZnCr&Z5@SiO2] shows an extremely higher p-X STY of 36.1 g p-x·kgcat -1·h-1, about eight times higher than that of [ZnCr&Z5]. DED manipulates ZnCr engine for methanol formation and drives FeMn engine for light olefins generation together, and then the formed methanol and light olefins are coordinately converted in situ into p-X-rich aromatics over Z5@SiO2. The DED model boosts the driving force for syngas/CO2 conversion, simultaneously concerting the cooperation of “dual-engine” for p-X generation, resulting in extremely high STY of p-X. This study achieves non-petroleum p-X production at industrial-relevant level and advances knowledge in designing innovative heterogeneous catalysts.

Abstract High-speed rails (HSRs) are a sustainable approach in many cities. Although some studies recognize that introducing HSR is negatively related to carbon emissions, explorations of the mechanisms underlying this relationship remain scarce. The main purpose of this study is to investigate whether introducing HSR reduces carbon emissions through increasing green innovation (GI) and the resilience of environmental investment (REI). Employing signal theory and fault tolerance theory, among others, we propose models that illuminate how inaugurating HSRs reduces carbon emissions through GI and REI. Our proposed central hypothesis is that GI and REI mediate carbon emission reduction by introducing HSR. In this study, we used the data from 284 China’s cities during 2000-2021 and examined our hypothesis via a difference-in-differences (DID) model. The results show that introducing HSR reduces carbon emissions through GI and REI. On the basis of the current status of China’s economic and social development, we further analyze several critical moderating effects, such as the digital economy, the urban‒rural gap, and whether it is a resource-based city. In 2023, China’s Central Economic Work Conference (CEWC) explicitly proposed “developing the digital economy.” We find that the digital economy strengthens the negative relationship between introducing HSRs and carbon emissions. The digital economy also strengthens the positive correlation between the introduction of HSR and GI. Additionally, this strengthens the positive correlation between HSRs and REI. In addition, the urban‒rural disparity is a manifestation of China’s uneven development. We find that the urban‒rural disparity weakens the relationship between HSRs and carbon emissions. In addition, China’s resource-based cities lag behind other cities. Our findings suggest that, in contrast to other cities, high-speed rails increase carbon emissions in resource-based cities.

Abstract Silicate has been proven to be highly-effective at immobilizing soil heavy metals, but the effects of silicate stabilizers on rice grain cadmium (Cd) reduction and rice quality under field conditions are not clear. In this study, a field experiment was conducted over three consecutive years was conducted to examine the Cd reduction in rice grains and to reveal the potential effects of silicate stabilizers on rice grain nutrients, by setting different amounts of bentonite (B), silica‒calcium fertilizer (SC) and zeolite powder (ZP). The results revealed that the application of the B, SC and ZP significantly decreased the soil CaCl2‒Cd concentration (> 39%) and significantly reduced the grain Cd concentration in both early rice (> 70%) and late rice (> 18%) under field conditions; the silicate stabilizers reduced the soil available iron (Fe) but did not limit rice grain Fe nutrition. Additionally, the three silicates promoted rice yield and improved the rice grain Ca and Mg contents; and the application of B increased the amylose concentration of the late rice grains. In conclusion, high amounts of silicate stabilizers did not adversely influence the soil conventional nutrient indices, rice minerals or rice taste, but changes in rice selenium content need attention. Overall, in comparison with lime, silicate stabilizers can improve not only the safety of rice but also the nutritional and taste qualities of rice and are more eco-friendly for long-term use in soil.

Abstract Neovaginas are surgically constructed to correct uterovaginal agenesis in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or as part of gender-affirming surgery for transfeminine individuals. Understanding the assembly of the neovaginal microbiota is crucial for guiding its management. To address this, we conducted a longitudinal study on MRKH patients following laparoscopic peritoneal vaginoplasty. Our findings reveal that the early microbial assemblage exhibited stochastic characteristics, accompanied with a notable bloom of Enterococcus faecalis and genital Mycoplasmas. While both the pre-surgery dimple microbiota and the fecal microbiota constituted the primary species pool, the neovaginal microbiota developed into a microbiota that resembled that of a normal vagina at 6–12 months post-surgery, albeit with a bacterial vaginosis (BV)-like structure. By 2–4 years post-surgery, the neovaginal microbiota had further evolved into a structure closely resembling with the homeostatic pre-surgery dimple microbiota. This concords with the development of the squamous epithelium in the neovagina and highlights the pivotal roles of progressive selective forces imposed by the evolving neovaginal environment and the colonization tropism of vaginal species. Notably, we observed that strains of Lactobacillus crispatus colonizing the neovagina primarily originated from the dimple. Since L. crispatus is generally associated with vaginal health, this finding suggests potential avenues for future research to promote its colonization.

Abstract. Background. The development of benign prostatic hyperplasia (BPH) is closely related to hypoxia in the prostatic stroma, and the hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway has been shown to significantly activate in response to hypoxia. The underlying mechanism for activation of this pathway in the pathogenesis of BPH remains unclear. Materials and methods. We constructed HIF-1α overexpression and knockdown BPH stromal (WPMY-1) and epithelial (BPH-1) cell lines, which were cultured under different oxygen conditions (hypoxia, normoxia, and hypoxia + HIF-1α inhibitor). Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were applied to detect the expression of the HIF-1α/VEGF pathway. Cell proliferation and apoptosis were analyzed by Cell Counting Kit-8 and flow cytometry. We used the miRWalk 2.0 database and Western blotting to predict the potential miRNA that selectively targets the HIF-1α/VEGF pathway, and verified the prediction by qPCR and dual-luciferase assays. Results. In a BPH stromal cell line (WPMY-1), the expression of VEGF was in accordance with HIF-1α levels, elevated in the overexpression cells and decreased in the knockdown cells. Hypoxia-induced HIF-1α overexpression, which could be reversed by a HIF-1α inhibitor. Moreover, the HIF-1α inhibitor significantly depressed cellular proliferation and promoted apoptosis in hypoxic conditions, assessed by Cell Counting Kit-8 and flow cytometry. However, in the BPH epithelial cell line (BPH-1), the expression level of HIF-1α did not influence the expression of VEGF. Finally, a potential miRNA, miR-17-5p, regulating the HIF-1α/VEGF pathway was predicted from the miRWalk 2.0 database and Western blotting, and verified by qPCR and dual-luciferase assay. Conclusions. In hypoxia, activation of the HIF-1α/VEGF pathway plays a crucial role in regulating cell proliferation in a BPH stromal cell line. Regulation by miR-17-5p may be the potential mechanism for the activation of this pathway. Regulation of this pathway may be involved in the pathogenesis of BPH.

Hydraulic fracturing is the primary method used for oilfield stimulation, and the migration and settlement pattern of proppant plays a crucial role in the formation of high conductivity propping fractures in the reservoir. This study summarizes two growth modes of sand dune: the ‘overall longitudinal growth’ mode and the ‘push growth along fracture length direction’ mode. To investigate these modes, a two-phase velocity test is conducted using PIV, and the exposure difference is utilized to separate the tracer and track the single-phase velocity. By analyzing the slickwater flow field and proppant velocity field, the micro-motion mechanism behind the two dune growth modes is quantitatively examined. The results indicate that mode 1 growth of the sand dune occurs when a pump with a large mesh number, high polymer viscosity, and large displacement is used. On the other hand, mode 2 growth is observed when a pump with a small mesh number, low polymer viscosity, and small displacement is employed. It is important to note that there is no clear boundary for the migration and sedimentation mode of proppant, as they can transition into each other under certain conditions. These modes only exist during specific stages of sand dune growth. In the case of the ‘backflow’ pattern, the settlement of proppant is primarily influenced by the vortex structure of slickwater. Conversely, in the ‘direct’ pattern, the proppant is propelled forward by the drag of the fluid and settles due to its own gravity. Once the proppant placement reaches equilibrium, the direction of proppant velocity follows a normal distribution within 0°. This approach establishes a connection between the overall placement of the sand dune and the microscopic movement of the proppant and slickwater. Optimizing construction parameters during fracturing construction can enhance the effectiveness of distal proppant placement in fractures.

In this study, nano-Nb-modified AlSi10Mg composites were fabricated using laser powder bed fusion (LPBF). The effects of Nb addition on the microstructure and mechanical properties of the AlSi10Mg alloy were systematically investigated. Compared with the as-built AlSi10Mg alloy, the microstructure along the building direction of the AlSi10Mg–Nb composites changed from coarse columnar grains to ultrafine equiaxed grains. Moreover, the preferential grain growth orientation was significantly weakened. Grain refinement occurs due to the presence of abundant in-situ Al3Nb precipitates dispersed within the grain, serving as heterogeneous nucleation inoculants. Simultaneously, the precipitation of NbSi2 particles along the eutectic network also contributed to refining the structure of the eutectic network. As a result, the LPBF-processed AlSi10Mg–Nb samples demonstrated a very high ultimate tensile strength (∼560 MPa) and good ductility (∼7%), comparable to those of high-strength aluminum alloys. The underlying mechanisms for this strength enhancement are discussed based on the improved mechanical properties. This study provides a novel perspective for the fabrication of high-performance AlSi10Mg alloys using LPBF.

Background: Fibrovascular scar healing of bone-tendon interface (BTI) instead of functional fibrocartilage regeneration is the main concern associated with unsatisfactory prognosis in rotator cuff repair. Mesenchymal stem cells (MSCs) exosomes have been reported to be a new promising cell-free approach for rotator cuff healing. Whereas, controversies abound in whether exosomes of native MSCs alone can effectively induce chondrogenesis. Purpose: To explore the effect of exosomes derived from low-intensity pulsed ultrasound stimulation (LIPUS)-preconditioned bone marrow mesenchymal stem cells (LIPUS-BMSC-Exos) or un-preconditioned BMSCs (BMSC-Exos) on rotator cuff healing and the underlying mechanism. Methods: C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to saline, BMSCs-Exos or LIPUS-BMSC-Exos injection therapy. Histological, immunofluorescent and biomechanical tests were detected to investigate the effect of exosomes injection on BTI healing and muscle fatty infiltration of the repaired rotator cuff. In vitro, native BMSCs were incubated with BMSC-Exos or LIPUS-BMSC-Exos and then chondrogenic/adipogenic differentiation were observed. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the chondrogenesis/adipogenesis-related miRNA profiles of LIPUS-BMSC-Exos and BMSC-Exos. The chondrogenic/adipogenic potential of the key miRNA was verified through function recover test with its mimic and inhibitor. Results: The results indicated that the biomechanical properties of the supraspinatus tendon-humeral junction were significantly improved in the LIPUS-BMSC-Exos group than that of the BMSCs-Exos group. The LIPUS-BMSC-Exos group also exhibited a higher histological score and more newly regenerated fibrocartilage at the repair site at postoperative 2 and 4 weeks and less fatty infiltration at 4 weeks than the BMSCs-Exos group. In vitro, co-culture of BMSCs with LIPUS-BMSC-Exos could significantly promote BMSCs chondrogenic differentiation and inhibit adipogenic differentiation. Subsequently, qRT-PCR revealed significantly higher enrichment of chondrogenic miRNAs and less enrichment of adipogenic miRNAs in LIPUS-BMSC-Exos compared with BMSC-Exos. Moreover, we demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-140, one of the most abundant miRNAs in LIPUS-BMSC-Exos. Conclusion: LIPUS-preconditioned BMSC-Exos can effectively promote BTI fibrocartilage regeneration and ameliorate supraspinatus fatty infiltration by positive regulation of pro-chondrogenesis and anti-adipogenesis, which was primarily through delivering miR-140. The translational potential of this article: These findings propose an innovative “LIPUS combined Exosomes strategy” for rotator cuff healing which combines both physiotherapeutic and biotherapeutic advantages. This strategy possesses a good translational potential as a local injection of LIPUS preconditioned BMSC-derived Exos during operation can be not only efficient for promoting fibrocartilage regeneration and ameliorating rotator cuff fatty infiltration, but also time-saving, simple and convenient for patients.

In this work, plasma electrolytic oxidation (PEO) with a fluoride-based electrolyte was performed on Mg-0.45Ca-xZn (x = 0, 0.45, 1.0, 2.0 wt%) alloys to enhance their degradation properties. These PEO coatings were composed of a porous layer and a barrier layer for alloys with Zn ≥ 0.45 wt%, while the coating on Mg-0.45Ca alloy was consisted of a dense inner layer and a porous outer layer. The content of Zn in the alloy has no significant effect on the hardness, adhesion strength and composition of the PEO coating. All coated-Mg-0.45Ca-xZn samples in this work showed decent anti-degradation properties in the simulated body fluid (SBF). Among them, PEO coatings on Mg-0.45Ca-1.0Zn and Mg-0.45Ca-2.0Zn alloys could provide excellent protection to the substrate over 3 months and exhibited good biocompatibility with Grade 0–1 of cytotoxicity, which were expected to be applied in the biomedical field. Besides, PEO process in this work enabled a high-quality coating to be formed on Mg–Ca–Zn bone screws.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Purpose – To optimize train operations, dispatchers currently rely on experience for quick adjustments when delays occur. However, delay predictions often involve imprecise shifts based on known delay times. Real-time and accurate train delay predictions, facilitated by data-driven neural network models, can significantly reduce dispatcher stress and improve adjustment plans. Leveraging current train operation data, these models enable swift and precise predictions, addressing challenges posed by train delays in high-speed rail networks during unforeseen events. Design/methodology/approach – This paper proposes CBLA-net, a neural network architecture for predicting late arrival times. It combines CNN, Bi-LSTM, and attention mechanisms to extract features, handle time series data, and enhance information utilization. Trained on operational data from the Beijing-Tianjin line, it predicts the late arrival time of a target train at the next station using multidimensional input data from the target and preceding trains. Findings – This study evaluates our model's predictive performance using two data approaches: one considering full data and another focusing only on late arrivals. Results show precise and rapid predictions. Training with full data achieves a MAE of approximately 0.54 minutes and a RMSE of 0.65 minutes, surpassing the model trained solely on delay data (MAE: is about 1.02 min, RMSE: is about 1.52 min). Despite superior overall performance with full data, the model excels at predicting delays exceeding 15 minutes when trained exclusively on late arrivals. For enhanced adaptability to real-world train operations, training with full data is recommended. Originality/value – This paper introduces a novel neural network model, CBLA-net, for predicting train delay times. It innovatively compares and analyzes the model's performance using both full data and delay data formats. Additionally, the evaluation of the network's predictive capabilities considers different scenarios, providing a comprehensive demonstration of the model's predictive performance.

ObjectivesWhen assessing the safety of the connectors of a multi-module offshore floating power generation platform, in order to compensate for the inability to carry out the real-time monitoring of the structural stress field across the whole domain due to a limited numbers of sensor, a digital twin method based on a simulation database is proposed that can rapidly predict the platform's stress field. MethodsBy downgrading the three-dimensional physical model of the connectors to a one-dimensional digital model, the stress field data is interpolated and deduced in digital space, thereby achieving the rapid prediction of the structural stress field across the whole domain and its visual display.ResultsThe results show that the simulation model is in good agreement with the test results, with a maximum absolute error of 8.61%; for the interpolation of data under different loading angles, when the interpolation step of the loading angle is 10°, the aver-age absolute error of stress is 1.98%; and for the interpolation of data under different loads, when the interpolation step of the load is 10 t, the average absolute error of stress is 1.28%, achieving the rapid prediction and visualization of the connectors' stress field distribution. Conclusions The digital twin-based model of connectors can provide useful references for the rapid dynamic perception and scientific prediction of the structural strength of offshore floating power generation platforms.

Abstract Although a number researchers have acknowledged that the aging population inhibits firm digital transformation, others find it promoting digital transformation in some firms. As the relevant literature to clarify such paradox is still scare, this paper wants to fill the gap regarding the labor cost theory, the capital-skill complementarity hypothesis, and the human capital externality theory. Based on the empirical tests of Chinese A-share listed companies from 2001 to 2022, this study detected a U-shaped relationship between the aging population and digital transformation. In terms of the institutional environment, higher marketization strengthens the U-shaped relationship by making the slopes on either side of it steeper. However, higher minimum wage levels weaken the U-shaped relationship. In terms of firm strategy, firms with stronger marketing capabilities strengthened the U-shaped relationship. However, firms with higher customer concentration weakened the U-shaped relationship. Overall, we enriched scholarly understanding of the impact of the aging population on digital transformation and demonstrated the dual potential impact of aging populations. Instead of assuming they are detrimental to the economy and society, positive contributions in the form of innovation and progress for companies can be detected.

Abstract Background Pneumoconiosis has a significant impact on the quality of patient survival. This study aims to evaluate the performance and application value of improved Unet network technology in the recognition and segmentation of lesion areas of lung CT images in patients with pneumoconiosis. Methods A total of 1212 lung CT images of patients with pneumoconiosis were retrospectively included. The improved Unet network was used to identify and segment the CT image regions of the patients’ lungs, and the image data of the granular regions of the lungs were processed by the watershed and region growing algorithms. After random sorting, 848 data were selected into the training set and 364 data into the validation set. The experimental dataset underwent data augmentation and were used for model training and validation to evaluate segmentation performance. The segmentation results were compared with FCN-8s, Unet network (Base), Unet (Squeeze-and-Excitation, SE + Rectified Linear Unit, ReLU), and Unet + + networks. Results In the segmentation of lung CT granular region with the improved Unet network, the four evaluation indexes of Dice similarity coefficient, positive prediction value (PPV), sensitivity coefficient (SC) and mean intersection over union (MIoU) reached 0.848, 0.884, 0.895 and 0.885, respectively, increasing by 7.6%, 13.3%, 3.9% and 6.4%, respectively, compared with those of Unet network (Base), and increasing by 187.5%, 249.4%, 131.9% and 51.0%, respectively, compared with those of FCN-8s, and increasing by 14.0%, 31.2%, 4.7% and 9.7%, respectively, compared with those of Unet network (SE + ReLU), while the segmentation performance was also not inferior to that of the Unet + + network. Conclusions The improved Unet network proposed shows good performance in the recognition and segmentation of abnormal regions in lung CT images in patients with pneumoconiosis, showing potential application value for assisting clinical decision-making.

Abstract Background Describing the transmission dynamics of infectious diseases across different regions is crucial for effective disease surveillance. The multivariate time series (MTS) model has been widely adopted for constructing cross-regional infectious disease transmission networks due to its strengths in interpretability and predictive performance. Nevertheless, the assumption of constant parameters frequently disregards the dynamic shifts in disease transmission rates, thereby compromising the accuracy of early warnings. This study investigated the applicability of time-varying MTS models in multi-regional infectious disease monitoring and explored strategies for model selection. Methods This study focused on two prominent time-varying MTS models: the time-varying parameter-stochastic volatility-vector autoregression (TVP-SV-VAR) model and the time-varying VAR model using the generalized additive framework (tvvarGAM), and intended to explore and verify their applicable conditions for the surveillance of infectious diseases. For the first time, this study proposed the time delay coefficient and spatial sparsity indicators for model selection. These indicators quantify the temporal lags and spatial distribution of infectious disease data, respectively. Simulation study adopted from real-world infectious disease surveillance was carried out to compare model performances under various scenarios of spatio-temporal variation as well as random volatility. Meanwhile, we illustrated how the modelling process could help the surveillance of infectious diseases with an application to the influenza-like case in Sichuan Province, China. Results When the spatio-temporal variation was small (time delay coefficient: 0.1–0.2, spatial sparsity:0.1–0.3), the TVP-SV-VAR model was superior with smaller fitting residuals and standard errors of parameter estimation than those of the tvvarGAM model. In contrast, the tvvarGAM model was preferable when the spatio-temporal variation increased (time delay coefficient: 0.2–0.3, spatial sparsity: 0.6–0.9). Conclusion This study emphasized the importance of considering spatio-temporal variations when selecting appropriate models for infectious disease surveillance. By incorporating our novel indicators—the time delay coefficient and spatial sparsity—into the model selection process, the study could enhance the accuracy and effectiveness of infectious disease monitoring efforts. This approach was not only valuable in the context of this study, but also has broader implications for improving time-varying MTS analyses in various applications.

Abstract Background To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. Methods Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. Results This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. Conclusion The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Abstract Background To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). Methods A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. Results In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. Conclusions Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery.

Abstract Background COVID-19 infections can result in severe acute respiratory distress syndrome (ARDS) requiring admission to the intensive care unit (ICU). Cardiovascular manifestation or exacerbation of cardiovascular diseases could be another complication. Cardiac arrhythmias including New-Onset Atrial Fibrillation (NOAF), have been observed in hospitalized patients with COVID-19 infections. In this analysis, we aimed to systematically compare the complications associated with NOAF in critically ill COVID-19 patients admitted to the ICU. Methods MEDLINE, EMBASE, Web of Science, the Cochrane database, http://www.ClinicalTrials.gov , Google Scholar and Mendeley were searched for relevant publications based on COVID-19 patients with NOAF admitted to the ICU. Complications including in-hospital mortality, ICU mortality, patients requiring mechanical ventilation, acute myocardial infarction, acute kidney injury, renal replacement therapy and pulmonary embolism were assessed. This is a meta-analysis and the analytical tool which was used was the RevMan software version 5.4. Risk ratios (RR) and 95% confidence intervals (CIs) were used to represent the data post analysis. Results In critically ill COVID-19 patients with NOAF admitted to the ICU, the risks of ICU mortality (RR: 1.39, 95% CI: 1.07 – 1.80; P = 0.01), in-hospital mortality (RR: 1.56, 95% CI: 1.20 – 2.04; P = 0.001), patients requiring mechanical ventilation (RR: 1.32, 95% CI: 1.04 – 1.66; P = 0.02) were significantly higher when compared to the control group without AF. Acute myocardial infarction (RR: 1.54, 95% CI: 1.31 – 1.81; P = 0.00001), the risk for acute kidney injury (RR: 1.31, 95% CI: 1.11 – 1.55; P = 0.002) and patients requiring renal replacement therapy (RR: 1.83, 95% CI: 1.60 – 2.09; P = 0.00001) were also significantly higher in patients with NOAF. Conclusions Critically ill COVID-19 patients with NOAF admitted to the ICU were at significantly higher risks of developing complications and death compared to similar patients without AF.

Abstract Background This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. Methods A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. Results Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. Conclusions The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

Abstract The sluggish kinetics of Volmer step in the alkaline hydrogen evolution results in large energy consumption. The challenge that has yet well resolved is to control the water adsorption and dissociation. Here, we develop biaxially strained MoSe2 three dimensional nanoshells that exhibit enhanced catalytic performance with a low overpotential of 58.2 mV at 10 mA cm−2 in base, and long-term stable activity in membrane-electrode-assembly based electrolyser at 1 A cm−2. Compared to the flat and uniaxial-strained MoSe2, we establish that the stably adsorbed OH engineer on biaxially strained MoSe2 changes the water adsorption configuration from O-down on Mo to O-horizontal on OH* via stronger hydrogen bonds. The favorable water dissociation on 3-coordinated Mo sites and hydrogen adsorption on 4-coordinated Mo sites constitute a tandem electrolysis, resulting in thermodynamically favorable hydrogen evolution. This work deepens our understanding to the impact of strain dimensions on water dissociation and inspires the design of nanostructured catalysts for accelerating the rate-determining step in multi-electron reactions.

The production of industrial chemicals with renewable biomass feedstock holds potential to aid the world in pursuing a carbon-neutral society. Trimellitic and trimesic acids are important commodity chemicals in industry that are prepared by the oxidation of petroleum-derived trimethylbenzene. To reduce the dependence on the limited oil source, we develop a potential sustainable alternative towards trimellitic and trimesic acids using biomass-based 2-methyl-2,4-pentandiol (MPD), acrylate and crotonaldehyde as starting materials. The process for trimellitic acid includes dehydration/D-A reaction of MPD and acrylate, flow aromatization over Pd/C catalyst, hydrolysis and catalytic aerobic oxidation (60% overall yield). The challenging regioselectivity issue of D-A reaction is tackled by a matched combination of temperature and deep eutectic solvent ChCl/HCO2H. Crotonaldehyde can also participate in the reaction, followed by Pd/C-catalyzed decarbonylation/dehydrogenation and oxidation to provide trimesic acid in 54% overall yield. Life cycle assessment implies that compared to conventional fossil process, our biomass-based routes present a potential in reducing carbon emissions.

In the field of autonomous driving, the accuracy and real-time requirements for 3D object detection technology continue to improve, which is directly related to the commercialization process and market popularity of autonomous vehicles. Despite the efficiency of pillar-based coding for onboard systems, it falls short in terms of accuracy and the reduction of incorrect positives. In this paper, we will examine how to solve the problem of high incorrect rate and low accuracy of existing methods. Firstly, a MAP coding module is introduced to optimize previous point cloud feature coding modules, allowing for the efficient extraction of fine-grained features from point cloud data. Then, we introduce an innovative sparse dual attention (SDA) to efficiently filter out irrelevant details in feature extraction, thereby improving the pertinence and efficiency of information extraction. Finally, to address the potential loss of information from single local feature extraction, a local and global fusion module (CTGC) is introduced. Our method has proactively demonstrated its efficiency and accuracy through rigorous experimentation across diverse datasets. Analysis of the results leads to the conclusion that our solutions provide accurate and robust detection results. Code will be available at https://github.com/lcy199905/MyOpenPCDet.git.

The production splitting coefficient is a key parameter for predicting gas production and reserves, evaluating gas recovery efficiency, and guiding the optimization of well patterns in multilayer commingled gas reservoirs. Therefore, developing a reliable splitting method to calculate this coefficient is critical for the development of multilayered commingled gas reservoirs. The gas drainage radius emerges as a key parameter in determining the production splitting coefficient grounded in the physical concept of production splitting. This coefficient is influenced by several factors—such as the wellbore radius, production layer thickness, porosity, initial gas saturation, gas deviation coefficient, reservoir temperature, gas drainage radius, and average formation pressure. Usually, calculating the gas drainage radius and average formation pressure cannot be performed in actual applications. Combining the gas well deliverability and material balance equations forms a closed-loop model for calculating the production splitting coefficient. This model features three equations with three unknowns—gas drainage radius, average formation pressure, and the production splitting coefficient. It introduces a double-cycle calculation method to solve the model. Specifically, the internal cycle computes the gas drainage radius, whereas the external cycle determines the production splitting coefficient, each offering unique solutions and employing alternating forward recursion and reverse recursion rules. The establishment of a double-cycle calculation process—defined by specific cycle step sizes and an error threshold—ensures that the external cycle progresses only upon the convergence of the internal cycle. Moreover, it determines whether the internal cycle can converge. Numerical simulations demonstrate that the production splitting coefficient exhibits different patterns across different production stage layers, highlighting the accuracy and mechanism soundness of the double-cycle method compared with direct numerical simulations. Moreover, it has good feasibility in field application because it can calculate the production splitting coefficient even without known values for gas drainage radius. Comparing gas-producing profiles indicates that the dual-cycle calculation method has reliable accuracy in field applications when the gas drainage radius and average formation pressure are unknown. Ultimately, the double-cycle calculation method offers a comprehensive solution for a three-element equation system, enabling simultaneous estimations of the production splitting coefficient, gas drainage radius, and average formation pressure.

Objectives: Bone and joint infections (BJI) pose formidable challenges in orthopaedics due to antibiotic resistance and the complexities of biofilm, complicating treatment. This comprehensive exploration addresses the intricate challenges posed by BJI and highlights the significant role of phage therapy as a non-antibiotic strategy. Methods: BJI, which encompass prosthetic joint infections, osteomyelitis, and purulent arthritis, are exacerbated by biofilm formation on bone and implant surfaces, hindering treatment efficacy. Gram-negative bacterial infections, characterized by elevated antibiotic resistance, further contribute to the clinical challenge. Amidst this therapeutic challenge, phage therapy emerges as a potential strategy, showing unique characteristics such as strict host specificity and biofilm disruption capabilities. Results: The review unveils the dynamics of phages, including their origins, lifecycle outcomes, and genomic characteristics. Animal studies, in vitro investigations, and clinical research provide compelling evidence of the efficacy of phages in treating Staphylococcus aureus infections, particularly in osteomyelitis cases. Phage lysins exhibit biofilm-disrupting capabilities, offering a meaningful method for addressing BJI. Recent statistical analyses reveal high clinical relief rates and a favourable safety profile for phage therapy. Conclusions: Despite its promise, phage therapy encounters limitations, including a narrow host range and potential immunogenicity. The comprehensive analysis navigates these challenges and charts the future of phage therapy, emphasizing standardization, pharmacokinetics, and global collaboration. Anticipated strides in phage engineering and combination therapy hold promise for combating antibiotic-resistant BJI.

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.

The self-assembly of Aβ peptides into toxic oligomers and fibrils is the primary cause of Alzheimer's disease. Moreover, the conformational transition from helix to sheet is considered a crucial step in the aggregation of Aβ peptides. However, the structural details of this process still remain unclear due to the heterogeneity and transient nature of the Aβ peptides. In this study, we developed an enhanced sampling strategy that combines artificial neural networks (ANN) with metadynamics to explore the conformational space of the Aβ42 peptides. The strategy consists of two parts: applying ANN to optimize CVs and conducting metadynamics based on the resulting CVs to sample conformations. The results showed that this strategy achieved better sampling performance in terms of the distribution of sampled conformations. The sampling efficiency is increased by 10-fold compared to our previous Hamiltonian Exchange Molecular Dynamics (MD) and by 1000-fold compared to ordinary MD. Based on the sampled conformations, we constructed a Markov state model to understand the detailed transition process. The intermediate states in this process are identified, and the connecting paths are analyzed. The conformational transitions in D23-K28 and M35-V40 are proven to be crucial for aggregation. These results are helpful in clarifying the mechanism and process of Aβ42 peptide aggregation. D23-K28 and M35-V40 can be identified as potential targets for screening and designing inhibitors of Aβ peptide aggregation.

Abstract: Given the threat of fossil fuel depletion, it is essential to proactively strive for carbon neutrality and promote clean, low-carbon and efficient energy use. This study used ERA5 reanalysis data to assess wind energy resources in the Pacific Northwest region. By analyzing key indicators such as wind power density, effective wind speed occurrence, and energy level occurrence, climate statistics and Empirical Orthogonal Function analysis (EOF) were used to examine the spatial distribution and long-term trend of offshore wind energy resources in the Northwest Pacific. The results suggest that there are abundant wind energy resources in this region, which are beneficial for the development of offshore wind energy. The rich areas are the East China Sea, Taiwan islands and reefs in the South China Sea and east of Japan, with prevailing wind power density (500 ∼ 2500 W/m2) and effective wind speed occurrence (80–90%) and energy level occurrence (60% ∼ 90%). Offshore wind energy resources in the Pacific Northwest are more abundant in fall and winter than in summer. The time coefficient of the first mode shows that the offshore wind energy in the Northwest Pacific has no obvious change trend, and the wind energy resources are relatively stable.

Abstract Background Health-related quality of life (HRQOL) in cancer patients has attracted increasing attention, which may be associated with self-rated health (SRH), anxiety, and depression. However, limited studies have focused on the mediating role of anxiety and depression in the relationship between SRH and HRQOL among cancer patients. Therefore, this study aims to explore the serial multiple mediating effects of anxiety and depression between SRH and HRQOL in cancer patients. Methods This cross-sectional study investigated a total of 565 hospitalized cancer patients in Anhui province in China from November 2020 to October 2021. SRH was assessed using a single-item measure, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) and HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D, three-level version). Socio-demographic and clinical characteristics were analyzed using descriptive statistics. The relationships between SRH, anxiety, depression, and HRQOL were evaluated by Pearson correlation analysis. The serial multiple mediation of anxiety and depression was assessed by SPSS PROCESS macro. Results SRH, anxiety, depression and HRQOL were significantly correlated(P

Abstract Background The heat shock transcription factor (Hsf) is a crucial regulator of plant stress resistance, playing a key role in plant stress response, growth, and development regulation. Results In this study, we utilized bioinformatics tools to screen 25 VbHsf members, which were named VbHsf1-VbHsf25. We used bioinformatics methods to analyze the sequence structure, physicochemical properties, conserved motifs, phylogenetic evolution, chromosome localization, promoter cis-acting elements, collinearity, and gene expression of Hsf heat shock transcription factor family members under low-temperature stress. The results revealed that the majority of the Hsf genes contained motif1, motif2, and motif3, signifying that these three motifs were highly conserved in the Hsf protein sequence of Verbena bonariensis. Although there were some variations in motif deletion among the members, the domain remained highly conserved. The theoretical isoelectric point ranged from 4.17 to 9.71, with 21 members being unstable proteins and the remainder being stable proteins. Subcellular localization predictions indicated that all members were located in the nucleus. Phylogenetic analysis of the Hsf gene family in V. bonariensis and Arabidopsis thaliana revealed that the Hsf gene family of V. bonariensis could be categorized into three groups, with group A comprising 17 members and group C having at least two members. Among the 25 Hsf members, there were 1–3 exons located on seven chromosome fragments, which were unevenly distributed. Collinearity analysis demonstrated the presence of seven pairs of homologous genes in the VbHsf gene family. The Ka/Ks ratios were less than one, indicating that the VbHsf gene underwent purification selection pressure. Additionally, nine genes in V. bonariensis were found to have collinearity with A. thaliana. Promoter analysis revealed that the promoters of all VbHsf genes contained various types of cis-acting elements related to hormones and stress. Based on RNA-seq data, qRT-PCR analysis of six highly expressed genes was performed, and it was found that VbHsf5, VbHsf14, VbHsf17, VbHsf18, VbHsf20 and VbHsf21 genes were highly expressed at 12 h of low-temperature treatment, and the expression decreased after 24 h, among which VbHsf14 was up-regulated at 12 h of low-temperature by 70-fold. Conclusions Our study may help reveal the important roles of Hsf in plant development and show insight for the further molecular breeding of V. bonariensis.

Abstract Background This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. Methods Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. Results Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. Conclusions HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. Trial registration This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.