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Abstract The early stages of embryonic development rely on maternal products for proper regulation. However, screening for functional maternal-specific factors is challenging due to the time- and labor-intensive nature of traditional approaches. Here, we combine a computational pipeline and F0 null mutant technology to screen for functional maternal-specific chromatin regulators in zebrafish embryogenesis and identify Mcm3l, Mcm6l, and Npm2a as playing essential roles in DNA replication and cell division. Our results contribute to understanding the molecular mechanisms underlying early embryo development and highlight the importance of maternal-specific chromatin regulators in this critical stage.

ObjectiveTo analyze the differences in the expressions of the total and phosphorylated proteins in human colon cancer HCT116 cells after the knockout (KO) of retinoic acid-induced protein 16 (RAI16) and explore the possible mechanism and related signaling pathways affecting its protein function in HCT116 cells. MethodsHCT116 KO and WT cell proteins were collected and extracted, and the protein extraction efficiency was detected via a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) experiment. After protein digestion, the peptides were labeled with TMT and analyzed via mass spectrometry. We used bioinformatics methods to analyze the identified differential proteins and differentially phosphorylated proteins by using GO, KEGG, and STRING databases. ResultsThe results of SDS-PAGE showed no evident protein degradation. In addition, some key bands were significantly different between the experimental and control groups. A total of 147 up-regulated and 230 down-regulated differential proteins were screened in accordance with the conditions of Foldchange≥1.5 or Foldchange≤1/1.5 and P

Abstract To assess the safety of varicella vaccine (VarV) by conducting post-marketing surveillance on adverse events following immunization (AEFI) in Jiangsu Province, China. Methods We utilized the AEFI Information System of mainland China to monitor and categorize adverse reactions associated with VarV. Results The incidence rate of AEFI was significantly higher after the first dose (48.79/100,000 doses) compared to the second dose (45.18/100,000 doses) (χ2 = 4.63, P = 0.031). Regional variations in AEFI incidence were observed within Jiangsu Province. Common reactions comprised 90.96% of AEFIs, while rare reactions and coincidental events accounted for 6.59% and 0.51%, respectively. Notably, there were no adverse events linked to vaccine quality, program errors, psychogenic reactions, or fatalities. Over 96% of AEFIs occurred within three days of VarV administration, with redness at the injection site (2.6 cm to 5 cm in diameter) being the most frequently observed symptom. Conclusion VarV demonstrates a commendable safety profile. Although there was a slight increase in AEFI incidence between 2022 and 2023, common vaccine reactions were predominantly observed, and the rates of rare reactions remained very low.

Abstract The dynamics of soft microparticles enclosed in a droplet flowing in a channel is an unexplored fundamental problem that lies at the heart of numerous applications, including droplet-based microfluidics, tissue engineering and smart material synthesis. Here we show that enclosing a flexible capsule into a droplet can amplify the capsule’s deformation parameters in channel flow by up to two orders of magnitude. Previously unreported capsule equilibrium shapes in channel flow, including an oblate spheroid and a reversed bullet, have also been discovered. We propose two theoretical models to predict the equilibrium position of the capsule inside the droplet, and estimate the capsule deformation, respectively. The present study provides an effective but simple approach to enhance and control the deformation of soft particles in a flowing suspension, which may inspire widespread applications, from high-throughput single-cell mechanical phenotyping, enhanced cross-membrane drug delivery, to manufacturing shape-controlled non-spherical particles and artificial cells.

Social media closely links virtual and real spaces, and this connection can influence the distribution of a city’s imagery hotspots. This study used point of interest data and site visit data from Tiktok to compare the characteristics of two spatial imagery hotspot types in Changsha as influenced by social media in terms of type characteristics, distribution pattern, and spatial relationships at both the macro- and meso-scales. Using methods such as buffer analysis, hotspot analysis, and bivariate spatial autocorrelation to research on imagery hotspot distribution, correlation, and differentiation in virtual – real spatial interaction, the result shows the following: 1) The impact of social media on different types of the city image is not balanced, having a greater impact on architectural landmarks and commercial consumption; 2) The distribution characteristics of image hotspots in virtual space and real space does not align, virtual space is more in line with the development strategy of cities; 3) Social media has a polarizing effect on city image, but is also less constrained by spatial form; 4) Social media has a certain restructuring effect on city image, and grouped city image in two spatial clustering types – enhanced and diminishing image spaces.

Abstract Background Although clinical guidelines exist for diagnosing abnormal uterine bleeding, there is a significant lack of agreement on the best management strategies for women presenting with symptom, particularly in diagnosing endometrial cancer. This study aimed to develop a preoperative risk model that utilizes demographic factors and transvaginal ultrasonography of the endometrium to assess and predict the risk of malignancy in females with endometrial cancer. Methods In this retrospective study, a logistic regression model was developed to predict endometrial carcinoma using data from 356 postmenopausal women with endometrial lesions and an endometrial thickness (ET) of 5 mm or more. These patients had undergone transvaginal ultrasonography prior to surgery, with findings including 247 benign and 109 malignant cases. The model’s predictive performance was evaluated using receiver operating characteristic (ROC) curve analysis and compared with post-surgical pathological diagnoses. Results Our model incorporates several predictors for endometrial carcinoma, including age, history of hypertension, history of diabetes, body mass index (BMI), duration of vaginal bleeding, endometrial thickness, completeness of the endometrial line, and endometrial vascularization. It demonstrated a strong prediction with an area under the curve (AUC) of 0.905 (95% CI, 0.865–0.945). At the optimal risk threshold of 0.33, the model achieved a sensitivity of 82.18% and a specificity of 92.80%. Conclusions The established model, which integrates ultrasound evaluations with demographic data, provides a specific and sensitive method for assessing and predicting endometrial carcinoma.

This research documents a new record of Miniopterus magnater in the south-western region of China, a significant discovery given the limited diversity of the Miniopterus genus within the country. Only three species of Miniopterus occur in China: Miniopterus magnater, Miniopterus fuliginosus and Miniopterus pusillus. These species share a high degree of morphological similarity, particularly in their external characteristics. This underscores the necessity for the identification of additional distinguishing traits that can aid in the taxonomic differentiation of these closely-related species.During the 2023 field expedition to various nature reserves in Yunnan Province, China, we encountered specimens of the genus Miniopterus. Utilising a combination of morphological assessments and phylogenetic analyses, we identified six individuals as Miniopterus magnater. A review of the existing geographical distribution data revealed that this species is primarily found in central and southern regions of China, with no previous records from the south-western part of the country. Based on our findings, we present a novel record of Miniopterus magnater's distribution in the south-western region of China.

Abstract Background Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein–Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. Objectives We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. Methods We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). Results The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47–0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15–0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83–0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56–0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31–0.87) and 49.0% (95% CI: 0.31–0.68), respectively. Conclusions This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

Abstract Aims/Introduction To evaluate the differences in cardiac autonomic function, cardiac structure and diastolic function between individuals with diabetic foot (DF) and those with diabetes but without DF. Materials and Methods A total of 413 individuals with DF and 437 without DF who underwent a 24‐h electrocardiogram Holter and a Doppler echocardiogram were included. The heart rate variability parameters to evaluate cardiac autonomic function, and the indices for the assessment of cardiac structure and left ventricular (LV) diastolic function, including left atrium, LV posterior wall thickness, interventricular septum and E/e′ ratio, were measured or calculated. Propensity score matching was used for the sensitivity analysis to minimize potential imbalance. Results In both the crude and propensity score matching analyses, significant differences were observed in heart rate variability between individuals with and without DF, as evidenced by lower standard deviation of the normal sinus interval, lower low‐frequency power/high‐frequency power ratio, lower standard deviation of the 5‐min average RR intervals, lower low‐frequency power, lower percentage of normal adjacent RR interval difference >50 ms, lower root mean square of successive RR interval differences and lower high‐frequency power (all P

In this work, the effect of tungsten inert gas (TIG) remelting on the microstructure, mechanical properties, and corrosion resistance of 5052 aluminum alloy joints produced by metal inert gas (MIG) welding is investigated. The results indicate that after TIG remelting of MIG welds, the proportion of dendrites increases in the remelted weld zone (WZ), porosity decreases by 76.9%, and the Fe elements in the second phase become coarser and more segregated. In contrast, the Mg elements form a solid solution with a decreased degree of segregation. In addition, the average grain size of the remelted structure decreases, while the proportion of sub-grain boundaries (SGBs) and the kernel average misorientation (KAM) values increase. Moreover, the heat-affected zone (HAZ) widens, and the grains become coarser. An increase of 4.5% in tensile strength and 20.0% in elongation was observed in the TIG-remelted joints after TIG remelting. Electrochemical and immersion tests on the TIG-remelted microstructure showed reduced corrosion resistance. Electrochemical tests mainly exhibited galvanic corrosion, resulting in the formation of pits. The types of corrosions observed in the immersion test differ from those in the electrochemical test, primarily exhibiting exfoliation corrosion and pitting corrosion. A higher geometric dislocation density (ρGND) in the structure increases the susceptibility to corrosion.

In Shendong mining area, there may be several abandoned roadways ahead of some mining faces due to the adjustment of the face layout. In order to avoid roof accidents when the mining face crossing abandoned roadways, the occurrence conditions of mining faces and abandoned roadways, mine pressure control methods and effects in Shendong mining area were summarized, and the mechanism of roof advance fracture when the working face crossing abandoned roadways was analyzed. With the consideration of the different supporting effects of abandoned roadways, pumping pillars, coal pillars and supports, numerical simulation was used to study the subsidence and bending tensile stress of the main roof under different coal pillar sizes, roof periodic fracture positions, widths of the abandoned roadways, and strength of the pumping pillars. Results show that with the inclined angle between the roadways and the working faces decreases from 90° vertical to 0° parallel, the advancing length of the working face affected by the abandoned roadways decreases, where the effect intensity increases. The mine pressure of working face when crossing the abandoned roadways is mainly control by the size of the coal pillar, the position of the previous roof periodic fracture before crossing the abandoned roadways, the width and the supporting strength of the abandoned roadways. Due to the inevitable failure of the coal pillars with the mining face approaches the abandoned roadways, and the width of the abandoned roadways is difficult to change, the strengthen supports of the abandoned roadways and waiting mine pressure before crossing the abandoned roadways are always adopted to prevent main roof from advance fracture in Shendong mining area. With the peak strength and elastic modulus of the pumping pillars increase, the roof of the abandoned roadways will be supported better, but the pumping pillars may failure under great load caused by the overlong roof hanging. If the adjacent twice roof periodic fracture occur before and after crossing the abandoned roadways, the main roof can bear most of the overlying load during crossing the abandoned roadways and the mine pressure can be controlled effectively. Otherwise, the advance fracture of the main roof will occur as well as the roof caving and supports crushing. Finally, the fully mechanized mining faces of Halagou coal mine in Shendong mining area are taking as examples, and the mine pressure control effects of pumping pillars and waiting mine pressure during the process of crossing the abandoned roadways were analyzed, which can provid reference for the mine pressure control when crossing the abandoned roadways in Shendong mining area and even other mines.

In order to determine the influence of anisotropy induced by primary bedding structure on fracture toughness and fracture process zone (FPZ) incubation characteristics of anthracite, the notched semi-circular bending (NSCB) anthracite samples with different bedding angles were subjected to the mode I three-point bending loading test on the MTS hydraulic servo test system. The incubation process of FPZ at crack tip was monitored by the digital image correlation method (DICM) combined with the acoustic emission (AE) localization technique. Based on the Irwin-Bazant model, the Strip-yield uniform traction model and the Strip-yield linear traction model, the fully developed FPZ length of anthracite samples were predicted and compared with the experimental results. The geometric morphology of anisotropic anthracite FPZ and the shear and tensile deformation time series of anthracite FPZ during its incubation at different bedding angles were discussed. The results show that the peak load, peak displacement and fracture toughness of anthracite increase with the increase of bedding inclination. Compared with the coal samples with the bedding angle of 0°, the average fracture toughness of the coal samples with the bedding angle of 22.5°, 45.0°, 67.5° and 90.0° increases by 6.76%, 86.82%, 85.47% and 134.46%, respectively. The FPZ length predicted by the Irwin-Bazant model and the Strip-yield uniform traction model is shorter than the test value, while the prediction of the Strip-yield linear traction model is generally higher than the test value. The estimation of FPZ length of anthracite by the Strip-yield uniform traction model is most close to the experimental value, indicating that the distribution of the cohesive force at the crack tip of the anthracite sample tends to be more uniform. The FPZ length of anthracite sample is proportional to the square of the ratio of fracture toughness and tensile strength: L∝(KIC/σt)2. The prefabricated crack tip deformation of the sample is dominated by tensile deformation and assisted by shear. The tensile deformation ranges from 27.71% to 57.26% Pmax, and the shear deformation ranges from 72.88% to 92.4% Pmax. The time of tensile deformation of the crack tip is superior to that of shear deformation. The strain field distribution on the circumferential measuring lines of the samples with the bedding angle of 0° and 45° is similar to the texture distribution of onion cross section, while the maximum principal strain monitoring value of the samples with the bedding angle of 90° shows a fluctuation and disordered distribution at most measuring angles. The strain gradient of anthracite sample is different on the divergence line of FPZ tip in each direction.

Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

Abstract Endoscopic submucosal dissection (ESD) of fibrotic colorectal lesions is difficult and has a high complication rate. There are only a few reports on the utility of orthodontic rubber band (ORB) traction in reducing the difficulty of this procedure. This study aimed to investigate the risk factors for perforation when applying ORB traction during ESD of fibrotic colorectal lesions. We continuously collected the clinical data of 119 patients with fibrotic colorectal lesions who underwent ESD with ORB and clip traction between January 2019 and January 2024. Possible risk factors for perforation were analyzed. The median ORB-ESD operative time was 40 (IQR 28–62) min, and the en bloc and R0 resection rates were 94.1% and 84.0%, respectively. Perforation occurred in 16 of 119 patients (13.4%). The lesion size, lesion at the right half of the colon or across an intestinal plica, the degree of fibrosis, operation time, and the surgeon’s experience were associated with perforation during ORB-ESD (P

Abstract Background Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant’s pathogenicity and reveal a patient’s genetic etiology. Methods The clinical data of a patient with HS who underwent genetic sequencing at the Children’s Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. Results A novel variant (c.301–2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301–2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. Conclusion We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.

Abstract Background In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. Methods We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. Results A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm’s suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. Conclusions The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.

High strength-ductility synergy is difficult to achieve in Nb alloys. Although high strength has been achieved through severe plastic deformation (SPD) technology, led to low ductility in alloys. In this work, FSP technology was applied to treat Nb–5W–2Mo–1Zr-0.1C (Nb521) alloys in preparation of fine-grained (FG)/ultrafine-grained (UFG) Nb521 with excellent strength and ductility. The microstructure evolution and mechanical property improvement mechanism were systematically studied for Nb521 alloy through various characterization pathways. The research results indicated that UFG Nb521 alloy with a grain size of 0.63 ± 0.41 μm can be prepared using low shoulder plunge depth FSP (LPD-FSP), which is the first report of UFG Nb521 alloy. The main reason for the formation of onion rings structure in SZ is the periodic wear of the stirring tool, and the onion rings structure does not cause mechanical damage. The texture formed by Nb521 alloy under different processing parameters is off-axis shear texture, which matches the ideal shear texture of D2 (112‾)[111] after rotation. In addition, this study also elaborated on the refinement mechanism of the second phase particles (Nb, Zr) C in Nb521 alloy during FSP. This study also indicated that the increase in yield strength of FSP samples at room temperature is mainly determined by grain refinement. These findings provided new ideas for the development of high-performance niobium alloys.

Abstract Chromosome rearrangements may distort 3D chromatin architectures and thus change gene regulation, yet how 3D chromatin structures evolve in insects is largely unknown. Here, we obtain chromosome-level genomes for four butterfly species, Graphium cloanthus, Graphium sarpedon, Graphium eurypylus with 2n = 30, 40, and 60, respectively, and Papilio bianor with 2n = 60. Together with large-scale Hi-C data, we find that inter-chromosome rearrangements very rarely disrupted the pre-existing 3D chromatin structure of ancestral chromosomes. However, some intra-chromosome rearrangements changed 3D chromatin structures compared to the ancestral configuration. We find that new TADs and subTADs have emerged across the rearrangement sites where their adjacent compartments exhibit uniform types. Two intra-chromosome rearrangements altered Rel and lft regulation, potentially contributing to wing patterning differentiation and host plant choice. Notably, butterflies exhibited chromatin loops between Hox gene cluster ANT-C and BX-C, unlike Drosophila. Our CRISPR-Cas9 experiments in butterflies confirm that knocking out the CTCF binding site of the loops in BX-C affected the phenotypes regulated by Antp in ANT-C, resulting in legless larva. Our results reveal evolutionary patterns of insect 3D chromatin structures and provide evidence that 3D chromatin structure changes can play important roles in the evolution of traits.

Abstract Background Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients. Methods The QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications. Results We recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P

Abstract Neuroinflammation caused by microglia and other immune cells plays pivotal role in cerebral ischemia/reperfusion injury and recovery. Modulating microglial polarization or Treg/Th17 balance from pro-inflammatory phenotype to anti-inflammatory phenotype are promising strategies for the treatment of cerebral ischemia. Curcumol has potential to fight against oxidative stress and inflammation, but whether it has protective effect in cerebral ischemia is uncertain. In the present study, cerebral ischemia was induced in C57BL/6 mice via middle cerebral artery occlusion (MCAO). MCAO mice were treated with curcumol for 7 days, then post-stroke ischemic injury, neurological deficits, microglial polarization and brain leukocyte infiltration were evaluated by TTC staining, behavioural tests, flow cytometry, western blot and immunofluorescence. We found that poststroke administration of curcumol reduced infarct volume, attenuated neuronal damage and inflammation, and improved motor function recovery of MCAO mice. Curcumol skewed microglial polarization toward anti-inflammatory phenotype in MCAO mice in vivo or after oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro. In addition, curcumol reduced local T cell infiltration in ischemic brain of MCAO mice and impaired Treg/Th17 balance. Curcumol inhibited ROS production and regulated Nrf2/HO-1 and NF-κB signaling in microglia. Finally, inhibiting Nrf2/HO-1 signaling or activating NF-κB signaling abrogated the influence of curcumol on microglial polarization. In conclusion, curcumol treatment reduced brain damage and neuroinflammation via modulating anti-inflammatory microglial polarization and Treg/Th17 balance through Nrf2/HO-1 and NF-κB signaling. Curcumol might be a promising treatment strategy for stroke patients.

Mpox is a zoonotic infectious disease caused by the mpox virus (MPXV). Historically, the majority of mpox cases have been documented in Central Africa. However, since May 2022, there has been a notable rise in reported cases from regions beyond Africa. Currently, over 110 countries spanning Europe, North America, South America, Asia, and other territories have reported mpox infections. This report details a case involving a patient who identifies as a man who has sex with men (MSM) and is concurrently infected with MPXV, human immunodeficiency virus type 1 (HIV-1), Pneumocystis jiroveci, as well as extensively drug-resistant tuberculosis (XDR-TB). This patient had also received a vaccination for smallpox in the past. Additionally, we provide photographic documentation charting the progression of dermatological manifestations associated with mpox. This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox. The rapid and widespread dissemination of the MPXV across various regions, especially among MSM communities, underscores the importance of enhancing preventive education efforts targeted at high-risk populations.

Abstract The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain. Graphical Abstract

A large-scale fine-grained Mg-Gd-Y-Zn-Zr alloy plate with high strength and ductility was successfully prepared by multi-pass friction stir processing (MFSP) technology in this work. The structure of grains and long period stacking ordered (LPSO) phase were characterized, and the mechanical properties uniformity was investigated. Moreover, a quantitative relationship between the microstructure and tensile yield strength was established. The results showed that the grains in the processed zone (PZ) and interfacial zone (IZ) were refined from 50 µm to 3 µm and 4 µm, respectively, and numerous original LPSO phases were broken. In IZ, some block-shaped 18R LPSO phases were transformed into needle-like 14H LPSO phases due to stacking faults and the short-range diffusion of solute atoms. The severe shear deformation in the form of kinetic energy caused profuse stacking fault to be generated and move rapidly, greatly increasing the transformation rate of LPSO phase. After MFSP, the ultimate tensile strength, yield strength and elongation to failure of the large-scale plate were 367 MPa, 305 MPa and 18.0% respectively. Grain refinement and LPSO phase strengthening were the major strengthening mechanisms for the MFSP sample. In particularly, the strength of IZ was comparable to that of PZ because the strength contribution of the 14H LPSO phase offsets the lack of grain refinement strengthening in IZ. This result opposes the widely accepted notion that IZ is a weak region in MFSP-prepared large-scale fine-grained plate.

We report the first record of Amolops truongi Pham, Pham, Ngo, Sung, Ziegler & Le, 2023 from China, based on four specimens collected in Yunnan Huanglianshan National Nature Reserve. This species was previously known only from the type locality in north-western Vietnam. Morphologically, the specimens from China correspond to the original description of A. truongi with a few variations and, phylogenetically, they are clustered with the type specimens of A. truongi from Vietnam with strong support. In this study, we also provide an updated diagnosis of this species combining the original description and new data.

Selenium (Se)-enriched Brassica napus L. is a valuable organic Se supplement. In this study, the fermentation broth enriched with organic Se (FFS) was prepared using Lactobacillus plantarum to ferment the substrate of Se-enriched Brassica napus L. Significant increases were observed after fermentation in total sugars, reducing sugars, soluble proteins, total phenolic content (TPC), and total flavonoid content (TFC). The organic Se was retained at a concentration of 54.75 ​mg/g in the freeze-dried sample. Principal component analysis and cluster analysis showed good separation between the FFS and unfermented (FS) groups. Fragrant 2-ethyloxetane had the highest content among all volatiles, while sinapine had the highest content among all phenolic compounds. The fermentation process showed remarkable improvement in the abundance and concentration of volatile compounds and phenolic contents, making FFS exhibit strong antioxidant activity and inhibitory capacity against α-glucosidase activity. The bioaccessibility of phenolic compounds was significantly greater in FFS compared to FS. ADMET analysis revealed that the majority of phenolic compounds contained in FFS did not exhibit mutagenicity toxicity, hepatotoxicity, skin sensitization, or blood-brain barrier penetration, indicating a favorable level of biosafety. Overall, our study provides a new insight into the further utilization of Se-enriched Brassica napus L. in foods.

Abstract The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients’ perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach’s α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P

Abstract The ruminal microbiota generates biogenic methane in ruminants. However, the role of host genetics in modifying ruminal microbiota‐mediated methane emissions remains mysterious, which has severely hindered the emission control of this notorious greenhouse gas. Here, we uncover the host genetic basis of rumen microorganisms by genome‐ and transcriptome‐wide association studies with matched genome, rumen transcriptome, and microbiome data from a cohort of 574 Holstein cattle. Heritability estimation revealed that approximately 70% of microbial taxa had significant heritability, but only 43 genetic variants with significant association with 22 microbial taxa were identified through a genome‐wide association study (GWAS). In contrast, the transcriptome‐wide association study (TWAS) of rumen microbiota detected 28,260 significant gene–microbe associations, involving 210 taxa and 4652 unique genes. On average, host genetic factors explained approximately 28% of the microbial abundance variance, while rumen gene expression explained 43%. In addition, we highlighted that TWAS exhibits a strong advantage in detecting gene expression and phenotypic trait associations in direct effector organs. For methanogenic archaea, only one significant signal was detected by GWAS, whereas the TWAS obtained 1703 significant associated host genes. By combining multiple correlation analyses based on these host TWAS genes, rumen microbiota, and volatile fatty acids, we observed that substrate hydrogen metabolism is an essential factor linking host–microbe interactions in methanogenesis. Overall, these findings provide valuable guidelines for mitigating methane emissions through genetic regulation and microbial management strategies in ruminants.

Exploring how environmental changes induce alterations in the phenology matching between plants and pollinators is significant for predicting species’ reproductive output and population dynamics. Our study focused on the invasive poisonous weed Stellera chamaejasme, widely distributed in the Qilian Mountains, China. By continuously monitoring its flowering phenology and flower visitors’ activities across different elevational ranges, we compared phenological matching patterns between S. chamaejasme and its potential pollinators across years with varying environmental temperatures. We found that S. chamaejasme, a typical early-flowering alpine species, begins its flowering in early June. Despite variations in the composition of flower-visiting insects across elevations and years, it maintained stable interactions with four major groups: Meloidae, Tachinidae, Scarabaeidae, and Noctuidae. Phenological mismatches between the peak flowering period of S. chamaejasme and the peak abundance of major potential pollinators were generally observed across its range, with higher phenological matching at higher elevations. This enhanced matching at higher elevations may drive the rapid invasion of S. chamaejasme in these areas. In the year with higher ambient temperature, phenological matching increased across its range, and its elevational sensitivity decreased, potentially contributing to its ongoing expansion in different elevations. The results of our study advance a new insight into the population expansion of invasive species in mountain ecosystems.

ObjectiveTo investigate the influencing factors of dysphagia in Alzheimer’s disease (AD) patients.MethodsThe study evaluated the demographic characteristics, nutritional status, social functioning, and swallowing dysfunction of 109 hospitalized AD patients.ResultsThe sample include 65.1% of female patients, mainly concentrate in >70 years old (72.5%). The illness duration is mainly 0~5 years (62.4%). After adjusting for confounding factors such as gender, poor lifestyle habits, illness duration, marital status, route to admission, concomitant medical illness, nutritional status, and social functioning, we find that the swallowing function in patients with AD is related to route to admission and concomitant medical illness (mainly includes: circulatory disease and respiratory disease). Age ≥90 years old and more concomitant medical illness contribute to a lower swallowing dysfunction score in patients with AD (P

BackgroundSchizophrenia, a severe mental disorder, is often complicated by Type 2 Diabetes Mellitus (T2DM), which can further impact patients’ psychological health. This study investigated the differences in eating attitudes, depression, and insight between schizophrenic patients with and without comorbid T2DM and explored the correlations among these factors to provide empirical support for clinical interventions.MethodsThis case-control study was conducted in Guangdong Province, China. From December 2022 to May 2023, a total of 300 hospitalized patients with schizophrenia (92 with comorbid T2DM and 208 without T2DM) were recruited. Data were collected using the Personal Information Form, Eating Attitudes Test (EAT-26), Hamilton Depression Scale (HAMD), and Insight and Treatment Attitudes Questionnaire (ITAQ). Statistical analyses, including t-tests, ANOVA, and multiple linear regression, were performed to examine differences and predictive factors of eating attitudes among patients. This study was approved by the Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University (approval number: 2020028), and written informed consent was obtained from all participants.ResultsPatients with schizophrenia and comorbid T2DM exhibited significantly higher risks of eating disorders (EAT-26: 12.54 ± 9.77 vs. 9.07 ± 7.90, P=0.003), more severe depression (HAMD: 14.71 ± 7.36 vs. 11.80 ± 6.04, P=0.001), and poorer insight (ITAQ: 10.46 ± 6.01 vs. 12.16 ± 6.09, P=0.025) compared to those without T2DM. Regression analysis revealed that gender, weekly exercise frequency, depression, and insight were significant predictors of eating attitudes among patients with T2DM. For patients without T2DM, weekly exercise frequency, smoking status, and insight were significant predictors.ConclusionSchizophrenic patients with comorbid T2DM are facing increasing risks related to eating attitudes, depression, and insight which highlight the need for targeted interventions. Regular psychological assessment and tailored support strategies might improve their mental health and quality of life. Future research should focus on longitudinal studies to clarify causal relationships and develop more effective interventions.

From January 2022 to November 2022, sporadic psittacosis occurred in Lishui city, China. The patients were presented with fever, cough, and pulmonary infiltration. Their clinical symptoms were not relieved after receiving cephalosporin, penicillin, beta-lactamase inhibitors, and quinolones. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples from the patients revealed Chlamydia psittaci infection. Then, three C. psittaci strains were isolated from the patients. Their whole genome sequences (WGSs) were obtained, and a core genome multilocus sequence typing (cgMLST) method was developed to study the population structure of C. psittaci. Using the constructed cgMLST method, 72 WGSs were divided into four related groups and ten sub-clusters. The Lishui strains formed a unique population of C. psittaci, which might represent a new variant of C. psittaci. In vitro antimicrobial susceptibility testing suggested that the Lishui strains were sensitive to tetracycline, macrolides, quinolones, and no drug-resistance was observed.

BackgroundMost studies have indicated that peripheral insulin-like growth levels factor-1 (IGF-1) is valuable in diagnosing heart failure, although the results have been inconsistent. To help solve the debate, we performed a meta-analysis to explore the relationship between IGF-1 and heart failure (HF).MethodsWe conducted an extensive search across various databases such as Embase, Cochrane Library, Pubmed, Medline, and Web of Science on May 30, 2023. From the extensive pool of studies, we selected 16 relevant articles, encompassing a total of 1,380 cases and 1,153 controls, to conduct a rigorous meta-analysis.ResultsThe total results indicated that there is an association between lower IGF-1 level and HF. The random-effects model yielded a pooled standardized mean difference (SMD) of −0.598 (95% CI: −1.081 to −0.116, P = 0.015). Further subgroup analysis also showed that IGF-1 levels were associated with HF in the age difference ≥5 years subgroup and body mass index difference >1 subgroup. Additionally, significant association between IGF-1 levels and HF were detected in the “serum” samples and “Europe” subgroups. Importantly, we observed IGF-1 showed significant lower levels in patients with reduced ejection fraction (HFrEF) compared to the controls, not in patients with preserved ejection fraction (HFpEF). The Begg’s and Egger’s tests revealed no indication of publication bias.ConclusionsOur meta-analysis has provided evidence suggesting a substantial correlation between reduced levels of IGF-1 and the occurrence of HF. Further prospective studies are necessary to ascertain the use of IGF-1 as a reliable biomarker for diagnosing HF, especially for HFrEF. But the diagnosis of HFpEF should be cautious.

BackgroundDiffuse connective tissue diseases (DCTDs) require long-term immunosuppressive treatment, increasing the risk of varicella-zoster virus (VZV) infection. This study aims to evaluate the humoral immune status against VZV in DCTD patients and explore factors that may influence their immune levels.MethodsThis is a retrospective cohort study that collected data from adult DCTD patients (≥18 years) attending our outpatient clinic. The geometric mean concentration (GMC) of VZV-specific IgG antibodies in the patients’ sera was measured using the enzyme-linked immunosorbent assay (ELISA).ResultsA total of 280 RA patients, 272 SLE + MCTD patients and 280 healthy controls were included. SLE + MCTD patients had significantly higher VZV IgG antibody levels than RA patients (p 0.05). Notable differences were observed particularly among female patients and those aged 30–49 years, (p

Abstract CRISPR‐based genomic‐imaging systems have been utilized for spatiotemporal imaging of the repetitive genomic loci in living cells, but they are still challenged by limited signal‐to‐noise ratio (SNR) at a non‐repetitive genomic locus. Here, an efficient genomic‐imaging system is proposed, termed CRISPR/Pepper‐tDeg, by engineering the CRISPR sgRNA scaffolds with the degron‐binding Pepper aptamers for binding fluorogenic proteins fused with Tat peptide derived degron domain (tDeg). The target‐dependent stability switches of both sgRNA and fluorogenic protein allow this system to image repetitive telomeres sensitively with a 5‐fold higher SNR than conventional CRISPR/MS2‐MCP system using “always‐on” fluorescent protein tag. Subsequently, CRISPR/Pepper‐tDeg is applied to simultaneously label and track two different genomic loci, telomeres and centromeres, in living cells by combining two systems. Given a further improved SNR by the split fluorescent protein design, CRISPR/Pepper‐tDeg system is extended to non‐repetitive sequence imaging using only one sgRNA with two aptamer insertions. Neither complex sgRNA design nor difficult plasmid construction is required, greatly reducing the technical barriers to define spatiotemporal organization and dynamics of both repetitive and non‐repetitive genomic loci in living cells, and thus demonstrating the large application potential of this genomic‐imaging system in biological research, clinical diagnosis and therapy.

Abstract The duck gastrointestinal tract (GIT) harbors an abundance of microorganisms that play an important role in duck health and production. Here, we constructed the first relatively comprehensive duck gut microbial gene catalog (24 million genes) and 4437 metagenome‐assembled genomes using 375 GIT metagenomic samples from four different duck breeds across five intestinal segments under two distinct rearing conditions. We further characterized the intestinal region‐specific microbial taxonomy and their assigned functions, as well as the temporal development and maturation of the duck gut microbiome. Our metagenomic analysis revealed the similarity within the microbiota of the foregut and hindgut compartments, but distinctive taxonomic and functional differences between distinct intestinal segments. In addition, we found a significant shift in the microbiota composition of newly hatched ducks (3 days), followed by increased diversity and enhanced stability across growth stages (14, 42, and 70 days), indicating that the intestinal microbiota develops into a relatively mature and stable community as the host duck matures. Comparing the impact of different rearing conditions (with and without water) on duck cecal microbiota communities and functions, we found that the bacterial capacity for lipopolysaccharide biosynthesis was significantly increased in ducks that had free access to water, leading to the accumulation of pathogenic bacteria and antibiotic‐resistance genes. Taken together, our findings expand the understanding of the microbiome signatures linked to intestinal regional, temporal development, and rearing conditions in ducks, which highlight the significant impact of microbiota on poultry health and production.

ObjectiveTo investigate the willingness and influencing factors of herpes zoster (HZ) vaccination among residents aged ≥40 years in Tengzhou city, Shandong province. MethodsA self-administered survey was conducted among 1 890 urban and rural residents aged 40 years and older in 21 towns/communities in Tengzhou city from May to July 2023, using multistage random sampling and a self-designed questionnaire. The study utilized a binary unconditional logistic regression model to examine the factors that affect the willingness to receive HZ vaccine. ResultsOf the 1 865 participants with valid questionnaire responses, 44.02% reported willingness to receive HZ vaccination and only 1.23% had received HZ vaccination. The results of multivariate logistic analysis showed that the participants with following characteristics were more likely to receive HZ vaccination: being female (odds ratio [OR] = 1.533, 95% confidence interval [95%CI]: 1.135 – 2.072), living in urban areas (OR = 1.899, 95%CI: 1.255 – 2.875), working in the medical field (OR = 1.828, 95%CI: 1.043 – 3.205), having a pension as their main income (OR = 2.252, 95%CI: 1.155 – 4.388) or being mainly supported by their children (OR = 2.181, 95%CI: 1.374 – 3.461), personal or peer history of HZ disease (OR = 47.768, 95%CI: 31.894 – 71.543) or uncertainty about personal history of HZ disease (OR = 1.646, 95%CI: 1.043 – 2.597), perceived severity of HZ disease (OR = 2.842, 95%CI: 1.974 – 4.092), knowledge of HZ vaccine (OR = 2.827, 95%CI: 2.048 – 3.903), having received COVID – 19 vaccine or other vaccines (OR = 3.335, 95%CI: 1.582 – 7.031), and tolerance to vaccine reactions (OR = 2.283, 95%CI: 1.583 – 3.292); whereas the participants who were self-employed were less likely to receive HZ vaccination (OR = 0.468, 95%CI: 0.260 – 0.840). ConclusionAmong the residents aged ≥ 40 years in Tengzhou city the willingness to receive HZ vaccination is relatively high, but the HZ vaccination rate is low; and the willingness is influenced by gender, place of residence, occupation, main source of income, personal or peer history of HZ disease, perceived severity of HZ disease, knowledge of HZ vaccine, vaccination history of COVID-19 vaccine and other vaccines, and tolerance to vaccine reactions.

Abstract Sexual dysfunction is common in males with chronic kidney disease (CKD), but yet the prevalence and specific relationship between CKD and sexual dysfunction, especially premature ejaculation (PE), remain to be investigated in China; This study aims to examine the prevalence and association between CKD and sexual dysfunction in male patients in China; In this cross-sectional, non-interventional, observational study conducted at a single center. 72 male patients with CKD were enrolled. Data collection included socio-demographic information, assessments via the 5-item version of the International Index of Erectile Function (IIEF-5), the Chinese version of the Premature Ejaculation Diagnostic Tool, the Patient Health Quentionnnaire-9 and the General Anxiety Disorder-7. Data analysis was performed using R version 3.5.2 and SPSS software version 25.0; Among the 72 CKD patients, 56.9% experienced erectile dysfunction and 29.2% had PE. Various factors including estimated Glomerular Filtration Rate, Albumin-to-Creatinine Ratio, psychological aspects, medication use were found to be associated with sexual dysfunction in these CKD patients; Sexual dysfunction is prevalent in males with CKD and is, influenced by multiple factors. It is important for clinicians to focus on sexual dysfunction in this patient group and further investigate its underlying mechanisms.

Abstract Organic room temperature phosphorescence (RTP) has significant potential in various applications of information storage, anti-counterfeiting, and bio-imaging. However, achieving robust organic RTP emission of the single-component system is challenging to overcome the restriction of the crystalline state or other rigid environments with cautious treatment. Herein, we report a single-component system with robust persistent RTP emission in various aggregated forms, such as crystal, fine powder, and even amorphous states. Our experimental data reveal that the vigorous RTP emissions rely on their tight dimers based on strong and large-overlap π-π interactions between polycyclic aromatic hydrocarbon (PAH) groups. The dimer structure can offer not only excitons in low energy levels for visible-light excited red long-lived RTP but also suppression of the nonradiative decays even in an amorphous state for good resistance of RTP to heat (up to 70 °C) or water. Furthermore, we demonstrate the water-dispersible nanoparticle with persistent RTP over 600 nm and a lifetime of 0.22 s for visible-light excited cellular and in-vivo imaging, prepared through the common microemulsion approach without overcaution for nanocrystal formation.

Abstract Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Abstract This study assesses the effect of stone content on the stability of soil–rock mixture slopes and the dynamics of ensuing large displacement landslides using a material point strength reduction method. This method evaluates structural stability by incrementally decreasing material strength parameters. The author created four distinct soil–rock mixture slope models with varying stone contents yet consistent stone size distributions through digital image processing. The initial conditions were established by linearly ramping up the gravity in fixed proportionate steps until the full value was attained. Stability was monitored until a sudden shift in displacement marked the onset of instability. Upon destabilization, the author employed the material point method to reconstruct the landslide dynamics. Due to the substantial computational requirements, the author developed a high-performance GPU-based framework for the material point method, prioritizing the parallelization of the MPM algorithm and the optimization of data structures and memory allocation to exploit GPU parallel processing capabilities. Our results demonstrate a clear positive correlation between stone content and slope stability; increasing stone content from 10 to 20% improved the safety factor from 1.9 to 2.4, and further increments to 30% and 40% ensured comprehensive stability. This study not only sheds light on slope stability and the mechanics of landslides but also underscores the effectiveness of GPU-accelerated methods in handling complex geotechnical simulations.

The BDI is a barometer of maritime trade, and the shipping trade network may graphically reflect trade pattern evolution. Because commerce influences freight prices, it is worthwhile to consider the influence of maritime network characteristics on freight rates. To begin, this article constructs maritime networks using AIS data and displays the dry bulk trade trend in the period following the pandemic. This will assist shipowners and laypeople in comprehending the evolution of dry bulk maritime commerce in the post-pandemic age. Second, the PVAR model is implemented in this work to investigate the connection between the trade in shipping mode and freight prices. The empirical study demonstrated that shipowners ought to devote more attention to port linkages, particularly significant ports in the maritime network in the years following the pandemic.

Abstract Background Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. Methods This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. Discussion This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. Trial registration ChiCTR1800017646.

Abstract Background Expanding new nurse training and education is a priority for nursing educators as well as a critical initiative to stabilize the nursing workforce. Given that there is currently no standardized program for the training of new nurses in China, we investigated the effectiveness of the bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary model combined with case-based learning ((BOPPPS-CBL) for the standardized training of new nurses. Methods The mixed method approach with explanatory sequential (quantitative-qualitative) method was used. A questionnaire was used to compare the impact of the BOPPPS-CBL model and the Traditional Learning Model (TLM) on the core competencies of 185 new nurses for two years of standardized training. Quantitative data were analyzed using SPSS 22.0. Focus group interviews were used with four groups of new nurses and perceptions of BOPPPS-CBL training were recorded. Qualitative data were analyzed thematically. Results According to the quantitative data, more new nurses agreed that the BOPPPS-CBL model stimulated their learning and improved their core nursing competencies than the TLM. The BOPPPS-CBL group outperformed the TLM group on theoretical knowledge tests. Qualitative data revealed that 87.5% of new nurses agreed on the value of BOPPPS-CBL training, and three themes were extracted: (1) role promotion; (2) formation of new thinking to solve clinical problems; and (3) suggestions for improvement. Conclusion BOPPPS-CBL training had a significant impact on improving new nurses’ core competencies and promoting the transition of new nurses to clinical practice nurses in China. The study recommends BOPPPS-CBL training as an effective teaching model for the standardized training and education of new nurses.

Monoterpenoids are typically present in the secretory tissues of higher plants, and their biosynthesis is catalyzed by the action of monoterpene synthases (MTSs). However, the knowledge about these enzymes is restricted in a few plant species. MTSs are responsible for the complex cyclization of monoterpene precursors, resulting in the production of diverse monoterpene products. These enzymatic reactions are considered exceptionally complex in nature. Therefore, it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid products. In our study, we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene products. By focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic, monocyclic and bicyclic products in MTSs, we observed that even a single amino acid mutation can change the specificity and diversity of MTS products, which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation changing. Notably, residues N340, I448, and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene cations. Alterations in these residues, either directly or indirectly, can impact the synthesis of single monoterpenes or their mixtures. By revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs, it will be possible to reasonably design and engineer different catalytic activities into existing MTSs, laying a foundation for the artificial design and industrial application of MTSs.

Abstract B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms underlying the therapeutic efficacy of CAR-T cells in these patients, longitudinal single-cell RNA and TCR sequencing was conducted on serial blood samples post infusion as well as their matching infusion products. By tracking the temporal evolution of CAR-T phenotypes, we demonstrated that proliferating cytotoxic-like CD8 clones were the main effectors in autoimmunity, whereas compromised cytotoxic and proliferation signature and profound mitochondrial dysfunction in CD8+ Te cells before infusion and subsequently defect CAR-T cells after manufacture might explain their characteristics in these patients. Our findings may guide future studies to improve CAR T-cell immunotherapy in autoimmune diseases.

Abstract Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Abstract The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.

Abstract Background and aims Metformin has been reported to inhibit the occurrence and development of colorectal cancer (CRC) by mediating changes in intestinal flora. Studies have also indicated that the occurence of familial adenomatous polyposis (FAP) may also be associated with changes in the intestinal flora. Therefore, we investigated the efficacy and safety of metformin in treating FAP and the association with intestinal flora. Results Compared with the baseline, the mean number and load of polyps in the areas of nanocarbon labeling and postoperative residuals in the test group were lower than those in the placebo group, while the diversity of intestinal flora species was increased. At the genus level, the relative abundance of g_Ruminococcus in the test group was lower than that at baseline, whereas the relative abundance of g_Lactobacillus was higher. These changes were statistically significant (P