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The research team has developed an information system based on clinical blood cell analysis and designed and implemented highly innovative algorithms. A neural network model was created based on these feature data of the blood cell population. Artificial intelligence algorithms can label susceptible populations for digestive tract cancer with an accuracy rate of over 80 %. A multi universe optimized BP neural network model was implemented based on TCGA data of common immune antigens in clinical laboratories. The working mechanism of this model is to assign values to the parameters of the BP neural network by using the process of searching for the best fitness in multiple universes. This model can predict the five-year survival rate of patients based on immunohistochemical data. Based on these data, an AI algorithm was used to develop a clinical prognostic model with an accuracy rate of over 99 %. The research team used single-cell sequencing data to locate cell subtypes in the features of immunohistochemical data, providing a biological basis for artificial intelligence models. The research team explored the potential biological mechanisms of cancer progression and occurrence based on gastrointestinal neuroendocrine products, and these algorithms have contributed to the prediction of cancer survival and incidence,team invented a simple and efficient algorithm.

Objective: To assess efficacy and safety of mirabegron 25 mg/day and 50 mg/day for overactive bladder in Chinese participants. Methods: Participants of ≥18 years with overactive bladder symptoms lasting for ≥12 weeks, a mean of ≥8 micturitions per 24 h, and a mean of at least one episode of Grade 3 or 4 urgency or urge incontinence per 24 h based on the Patient Perception of Intensity of Urgency Scale over a 3-day micturition diary period were randomized 2:1 to open-label treatment with oral mirabegron 50 mg or 25 mg once daily for 12 weeks (15 sites in China, January 2021–March 2022). A dose escalation from 25 mg/day to 50 mg/day was permitted at weeks 4 and 8 according to the investigators' discretion. The primary efficacy endpoint was the change from baseline to Week 12 in the mean number of micturitions per 24 h in those randomized to mirabegron 50 mg/day. Secondary efficacy endpoints were the change in mean number of micturitions at weeks 4 and 8 in the mirabegron 50 mg/day group and weeks 4, 8, and 12 in the mirabegron 25 mg/day group, change from baseline to weeks 4, 8, and 12 in Grade 3 or 4 urgency episodes on the Patient Perception of Intensity of Urgency Scale, episodes of daytime incontinence, nighttime incontinence, and urgency incontinence, and Overactive Bladder Symptom Score for mirabegron 50 mg/day and 25 mg/day groups. Results: Statistically significant reduction (p

Abstract Black carp (Mylopharyngodon piceus) is one of the “four famous domestic fishes” in China and an important economic fish in freshwater aquaculture. A high-quality genome is essential for advancing future biological research and breeding programs for this species. In this study, we aimed to generate a high-quality chromosome-level genome assembly of black carp using Nanopore and Hi-C technologies. The final genome assembly was 848.70 Mb in length, with a contig N50 of 3.37 Mb and a scaffold N50 of 34.13 Mb. The genome was anchored onto 24 chromosomes by Hi-C technology. The BUSCO (Benchmarking Universal Single-Copy Orthologs) completeness score of the genome assembly is 97.6% when compared to the Actinopterygii_odb10 database. In total, 203.54 Mb of repeat sequences and 37,418 protein-coding genes were predicted in the genome assembly. Taken together, our study provides a chromosome-level genome assembly, which can serve as a valuable genetic resource to support further biological studies and breeding efforts of black carp.

Abstract Objectives To evaluate the efficacy and safety of a non-invasive low-frequency tibial nerve stimulator (TNS-01) vs sham control in relieving the symptoms of overactive bladder (OAB) patients. Patients Participants who were diagnosed with primary OAB or exhibited at least one OAB symptom. All participants underwent three 30-min intervention sessions weekly. Methods The subjects were 1:1randomized (block randomization with a block size of 4) to either active treatment (TNS-01 group) or sham treatment (sham group). Based on the randomization, the subject will be given either an active or sham device system (systems will only differ in the Instructions for Use and electrode size/shape). During the 12-week study period, all participants underwent three 30-min intervention sessions weekly. The primary endpoint was the change in Overactive Bladder Symptom Score (OABSS) at week 12 from the baseline. Results Of the 109 recruited OAB patients. In the TNS-01 group, the OABSS change from baseline at week 12 was significantly higher than that in the sham group (2.83 ± 2.53 vs 1.62 ± 2.59, p = 0.02). The absolute and percent changes of average UUI episodes per day from baseline at week 8 in the TNS-01 group were significantly lower from those in the sham group (0.11 ± 1.33 vs 0.68 ± 2.14, p = 0.01; − 27.82% ± 167.33% vs 87.18% ± 25.20%, p = 0.04). One treatment-related adverse event (hematuria) was reported by one patient (1.8%) in the sham group. Conclusions The TNS-01 device is effective and safe in relieving OAB symptoms after 12 weeks of stimulation. Trial registration number: NCT04999657.

Abstract Background Several approaches are being explored for engineering off-the-shelf chimeric antigen receptor (CAR) T cells. In this study, we engineered chimeric Fcγ receptor (FcγR) T cells and tested their potential as a versatile platform for universal T cell therapy. Methods Chimeric FcγR (CFR) constructs were generated using three distinct forms of FcγR, namely CD16A, CD32A, and CD64. The functionality of CFR T cells was evaluated through degranulation assays, specific target lysis experiments, in vitro cytokine production analysis, and assessment of tumor xenograft destruction specificity in mouse models using different monoclonal antibodies (MoAbs). Results Three types of CFR T cells were engineered, 16s3, 32-8a, 64-8a CFR T cells. In the presence of rituximab (RTX), cytotoxicity of all three types of CFR T cells against CD20+ Raji-wt, K562-CD20+, and primary tumor cells was significantly higher than that of the mock T cells (P

This study takes the mining of B1+2 and B3-6 coal seams in the southern mining area of a steep and thick coal seam mine as the engineering background, and combines theoretical analysis and numerical simulation methods to compare and study the effects of horizontal and inclined segmented mining of steep and thick coal seams on the prevention and control of rock burst. The results show that: before mining the B3-6 seam at the same level, the stress concentration area of horizontal sectional mining is mainly located in the surrounding rock above and below the roadway and the coal body below the gob, while the stress concentration area of inclined sectional mining is shifted to the coal body at the sharp corner area below the gob and the surrounding rock above and below the roadway at the low level side; compared with horizontal sectional mining, the peak stress in the surrounding rock above and below the high level side roadway of inclined sectional mining is reduced by 10-20 MPa, and the stress concentration roadway is reduced from 4 to 2; mining the B3-6 coal seam first at the same level can weaken the horizontal stress transfer, and it has the function of pressure relief protection for the B1+2 coal seam mined later. In addition, under the condition of inclined sectional mining, the inclined gob can further weaken the horizontal stress transfer, and it has the function of pressure relief protection for the high level side roadway; based on comprehensive comparison, it is believed that the stress level of the surrounding rock above and below the roadway is lower and the degree of deformation of the roadway is the lowest, which is more conducive to the prevention and control of rock burst.

Abstract To investigate the effect of the filter device on the cleanliness of molten steel and the flow field distribution within the tundish. The tundish filters were designed into five groups of pores with 20°, 25°, 30°, 35° and 40° elevation angles, and the flow field distribution and impurity removal rate of molten steel were calculated by Discrete Phase Model (DPM). The results showed that the removal rate of impurity in the molten steel could be significantly improved by using the tundish filter with elevation angle. When the elevation angle of the filter was 40°, the impurity removal rate reached 74.05%, and the flow field distribution would be more stable. The presence of the tundish filter caused the higher flow density of the molten steel before the filter inlet to decrease and become steadier after the filter, thereby enhancing the contact rate between impurities in the molten steel and the covering agent, ultimately achieving the highest impurity removal rate.

Abstract The deck-charge structure, also known as axially decoupled charge structure, has been widely applied in open-pit rock excavation to improve blasting performance. However, the relationships between blast-induced fragmentation and deck-charge structures remain not well understood. This paper aims to experimentally investigate the influences of deck ratio, deck position and deck material on blast-induced fragmentation. Concrete specimens with dimension of 400 × 400 × 200 mm3 were used for small-scale single-hole blasting experiments. The dynamic fracturing process under blast loading was recorded with a high-speed camera. Displacement and strain fields were analyzed employing a 3D digital image correlation (DIC) system, and the fragment size distribution (FSD) was quantified through ImageJ, an advanced image-processing tool. The borehole wall pressure (BWP) was monitored through the embedded PVDF gauges within the test specimens. The results indicate that during deck charge blasting, the host concrete undergoes three phases: crushing, further crushing and fracturing, and radial crack development. Fragmentation performance improves within an optimal air-deck ratio range, while excessive ratios lead to poorer fragmentation compared to fully coupled charge blasting. The center deck charge yields the superior fragmentation, followed by double-ends and top deck charges. Water-deck charge generates finer fragmentation than air deck and polyethylene (PE) deck charges. Expanded polystyrene (EPS) deck charge does not facilitate fragmentation but may reduce vibration and limit damage to the remaining rock mass. Based on experiment results, production blasts with fully coupled charge, center air-deck charge and center water-deck charge were performed in an open-pit mine. These field tests revealed that the proposed center deck charge blasting reduced median fragment size by at least 15%, with the center water-deck charge demonstrating superior fragmentation by maximizing explosive energy utilization for rock fracturing.

ABSTRACT Functional groups (FGs) represent a classification scheme designed to study the ecological adaptations of phytoplankton. However, FG dynamics studies in phytoplankton are often conducted independent of taxonomic studies, so the factors influencing community dynamics have not been sufficiently investigated or compared between the two classification systems. In this study, we compared the intricate relationship between taxonomic and FG compositions in North China lakes and delve into the key environmental drivers shaping phytoplankton community dynamics. This investigation revealed that taxonomic and FG classifications exhibit high qualitative and quantitative similarities in the community structure. Environmental drivers had a stronger influence on the FG structure than taxonomic composition, indicating that the FG classification does not result in the loss of ecological information regarding the community structure, even with the reduced number of grouping units. Indeed, it was evident that FGs contained a larger quantity of ecological information. These conclusions were further verified using lakes in eastern China. Additionally, we found that climatic–geographical factors usually exerted indirect influences, by altering water chemistry, while water chemical factors had more direct and stronger influences. The combined effects of both types of environmental factors had a greater impact on the phytoplankton FG structure than on taxonomic composition. In conclusion, we believe that an in‐depth study of FGs will better focus on the ecological characteristics of phytoplankton, while also avoiding the need for extensive species identification.

Abstract The application of classic foaming agent faces several issues, including excessive use of defoaming agent, inadequate defoaming, pipeline blockage due to silicone oil precipitation, and high development cost of the foaming agent. To address the aforementioned issues, a novel intelligent foaming agent was created. This resulted in the development of a new intelligent foaming and discharging agent system. The study focused on analyzing key performance indicators of the foaming agent system, including temperature resistance, salt resistance, oil resistance, phase transition temperature point, foaming ability, foam half-life, liquid carrying capacity, and self-defoaming ability. The experimental findings indicate that TS-1 and ESAB exhibit favorable foaming performance and stability under the conditions of 90 °C temperature, 20 × 104 mg/L salinity, and 40% condensate oil content after a 1:1 mixture. Additionally, they are capable of undergoing phase transition within the temperature range of 12 to 15.2 °C. The Waring blender stirring method resulted in the foaming agent solution, which had a concentration of 3 g/L, reaching a volume of 487 mL. The foam’s half-life was 20 min, and the liquid carrying rate was 91.7%. After a duration of 20 min, the rate of self-defoaming was 81.6%. The addition of the self-developed synergist facilitated the defoaming process, which was successfully accomplished within a time frame of 10 min. Moreover, the self-defoaming rate achieved a remarkable 100%. The foam drainage agent system may autonomously react to variations in ambient temperature and achieve phase transition behavior through temperature stimulation. This is accomplished by utilizing the natural temperature difference between the bottom hole and the wellhead during foam drainage gas recovery operations. This innovation presents a novel concept for the foam drainage agent used in recovering drainage gas. It simplifies the operation of gas recovery in oil and gas wells, provides solutions for further smartening up oil and gas fields. It holds immense theoretical and practical importance.

Abstract Due to the sensitivity of the shaped charge jet to standoff and the complexity of its impact under lateral disturbances, this study aims to investigate the dynamic impact evolution of the jet influenced by standoff and lateral disturbances. A finite element model for the dynamic impact of shaped charge jets was established. Dynamic impact experiments were designed and conducted to validate the effectiveness of the numerical simulations. Utilizing dimensional analysis, a predictive model was developed for jet dynamic impact considering the combined effects of target plate strength, standoff and lateral disturbances. The results indicate that as the standoff varies between 90 mm and 225 mm, the dynamic impact depth of the jet decreases approximately linearly with increasing standoff. Meanwhile, for lateral disturbance velocities ranging from 100 m/s to 400 m/s, the impact depth decreases exponentially with increasing lateral relative velocity of the target. The lateral disturbance velocity is identified as the primary factor influencing jet impact, while the standoff is a secondary factor. The agreement among computational results, numerical simulations, and experimental outcomes confirms the accuracy and effectiveness of the predictive model and simulations, providing a basis for evaluating the dynamic impact potential of shaped charges.

Abstract Background The objective of this study is to investigate the potential association between change in body composition before and after cetuximab-based therapy and the prognostic outcomes among individuals diagnosed with advanced colorectal cancer. Methods A retrospective analysis was undertaken on a cohort of 81 patients diagnosed with RAS wild-type (WT) metastatic colorectal cancer (mCRC) who were treated with cetuximab-based first-line therapy. To assess relevant body composition parameters, quantitative computed tomography (QCT) scans were conducted both before and after cetuximab treatment. These parameters encompassed measurements of visceral fat area (VFA), subcutaneous fat area (SFA), total muscle area (TMA) at the third lumbar vertebra level (L3), and bone mineral density (BMD) at the first and second vertebrae levels (L1/2). The skeletal muscle index (SMI) was subsequently calculated, and changes in parameters (∆VFA, ∆SFA, ∆SMI, ∆BMD) were standardized. Results The cut-off values for ∆VFA, ∆SFA, ∆SMI, and ∆BMD were 0.28%, -2.76%, -2.97%, and -7.98%, respectively. CEA, ∆VFA, ∆SMI, and ∆BMD were associated with poor outcomes of cetuximab-based first-line chemotherapy (P

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Macrophages are abundant in the tumor microenvironment, making them an attractive target for therapeutic intervention. While current immunotherapies, including immune checkpoint inhibition (ICI) and chimeric antigen receptor T (CAR-T) cells, have shown limited efficacy in pancreatic cancer, a novel approach involving chimeric antigen receptor macrophages (CAR-M) has, although promising, not been explored in pancreatic cancer. In this study, we first investigated the role of CAR-M cells targeting c-MET in pancreatic cancer. Methods The effectiveness and rationality of c-MET as a target for CAR-M in pancreatic cancer were validated through bioinformatic analyses and immunohistochemical staining of samples from pancreatic cancer patients. We utilized flow cytometry and bioluminescence detection methods to demonstrate the specific binding and phagocytic killing effect of CAR-M on pancreatic cancer cells. Additionally, we observed the process of CAR-M engulfing pancreatic cancer cells using confocal microscopy and a long-term fluorescence live cell imaging system. In an in situ tumor model transplanted into NOD/SCID mice, we administered intraperitoneal injections of CAR-M to confirm its inhibitory function on pancreatic cancer. Furthermore, we validated these findings in human monocyte-derived macrophages (hMDM). Results Bioinformatics and tumor tissue microarray analyses revealed significantly higher expression levels of c-MET in tumor tissues, compared to the paired peritumoral tissues, and higher c-MET expression correlated with worse patient survival. CAR-M cells were engineered using human monocytic THP-1 cell line and hMDM targeting c-MET (CAR-M-c-MET). The CAR-M-c-MET cells demonstrated highly specific binding to pancreatic cancer cells and exhibited more phagocytosis and killing abilities than the pro-inflammatory polarized control macrophages. In addition, CAR-M-c-MET cells synergized with various cytotoxic chemotherapeutic drugs. In a NOD/SCID murine model, intraperitoneally injected CAR-M-c-MET cells rapidly migrated to tumor tissue and substantially inhibited tumor growth, which did not lead to obvious side effects. Cytokine arrays and mRNA sequencing showed that CAR-M-c-MET produced higher levels of immune activators than control macrophages. Conclusions This study provides compelling evidence for the safety and efficacy of CAR-M therapy in treating pancreatic cancer. The results demonstrate that CAR-M-c-MET significantly suppresses pancreatic cancer progression and enhances the effectiveness of cytotoxic chemotherapy. Remarkably, no discernible side effects occur. Further clinical trials are warranted in human pancreatic cancer patients.

The thermostable α-amylase derived from Bacillus licheniformis (BLA) has multiple advantages, including enhancing the mass transfer rate and by reducing microbial contamination in starch hydrolysis. Nonetheless, the application of BLA is constrained by the accessibility and stability of enzymes capable of achieving high conversion rates at elevated temperatures. Moreover, the thermotolerance of BLA requires further enhancement. Here, we developed a computational strategy for constructing small and smart mutant libraries to identify variants with enhanced thermostability. Initially, molecular dynamics (MD) simulations were employed to identify the regions with high flexibility. Subsequently, FoldX, a computational design predictor, was used to design mutants by rigidifying highly flexible residues, whereas the simultaneous decrease in folding free energy assisted in improving thermostability. Through the utilization of MD and FoldX, residues K251, T277, N278, K319, and E336, situated at a distance of 5 Å from the catalytic triad, were chosen for mutation. Seventeen mutants were identified and characterized by evaluating enzymatic characteristics and kinetic parameters. The catalytic efficiency of the E271L/N278K mutant reached 184.1 g L−1 s−1, which is 1.88-fold larger than the corresponding value determined for the WT. Furthermore, the most thermostable mutant, E336S, exhibited a 1.43-fold improvement in half-life at 95 ℃, compared with that of the WT. This study, by combining computational simulation with experimental verification, establishes that potential sites can be computationally predicted to increase the activity and stability of BLA and thus provide a possible strategy by which to guide protein design.

To study the effects of radio frequency-assisted hot air drying (RFHAD) on the quality of South American white shrimp (Penaeus vannamei), the RFHAD process based on the dielectric properties of the shrimp was optimized. The effects of radio frequency drying (RFD) and RFHAD on the flavor nucleotide contents and equivalent umami levels in dried shrimp were compared with those of hot-air drying (HAD). The results showed that as the temperature and moisture content increased, the dielectric constant and loss factor of the shrimp also increased, facilitating moisture migration and enhancing the drying rate. The penetration depth of the RFD was negatively correlated with moisture content, temperature, and frequency. Additionally, increasing the number of stacked layers and reducing the plate spacing significantly increased the drying rate of the shrimp (P

The genus Hydrurus contains a solitary species, Hydrurus foetidus. Its thalli exhibit a remarkable structure, consisting of a firm central axis surrounded by peripheral branches, all enveloped within a viscous, gelatinous coating. Molecular data pertaining to the genus Hydrurus are scarce, necessitating further investigation into its phylogenetic relationships.A new site with benthic freshwater alga Hydrurus foetidus (Villars) Trevisan has been discovered in the Fenhe River in Shanxi Province, China. The physical and chemical parameters of water were meticulously measured and documented. Detailed morphological observations were conducted on the specimen, measuring different cell categories. The SSU, LSU, ITS and rbcL DNA sequence data of H. foetidus collected from Shanxi were determined. An extensive three-gene phylogenetic tree was constructed, revealing a strong relationship between the specimen in this study and H. foetidus specimen from Norway. Time-calibrated molecular phylogenetic analysis further indicated that the genus Hydrurus diverged approximately 125 million years ago (Early Cretaceous), while the two H. foetidus strains from Shanxi, China and Norway diverged approximately 6 million years ago (Neogene). The results of this study supplement new molecular evidence for H. foetidus and contribute significantly to our understanding of the geographical distribution and evolutionary history of the genus Hydrurus.

Abstract This study was performed to investigate the diagnostic value of radiomics models constructed by fat suppressed T2-weighted imaging (T2WI-FS) and contrast-enhanced T1-weighted imaging (CET1) based on magnetic resonance imaging (MRI) for differentiation of osteosarcoma (OS) and chondrosarcoma (CS). In this retrospective cohort study, we included all inpatients with pathologically confirmed OS or CS from Second Xiangya Hospital of Central South University (Hunan, China) as of October 2020. Demographic and imaging variables were extracted from electronic medical records and compared between OS and CS group. Totals of 530 radiomics features were extracted from CET1 and T2WI-FS sequences based on MRI. The least absolute shrinkage and selection operator (LASSO) method was used for screening and dimensionality reduction of the radiomics model. Multivariate logistic regression analysis was performed to construct the radiomics model, and receiver operating characteristic curve (ROC) was generated to evaluate the diagnostic accuracy of the radiomics model. The training cohort and validation cohort included 87 and 29 patients, respectively. 8 CET1 features and 15 T2WI-FS features were screened based on the radiomics features. In the training group, the area under the receiver-operator characteristic curve (AUC) value for CET1 and T2WI-FS sequences in the radiomics model was 0.894 (95% CI 0.817–0.970) and 0.970 (95% CI 0.940–0.999), respectively. In the validation group, the AUC value for CET1 and T2WI-FS sequences in the radiomics model was 0.821 (95% CI 0.642–1.000) and 0.899 (95% CI 0.785–1.000), respectively. In this study, we developed a radiomics model based on T2WI-FS and CET1 sequences to differentiate between OS and CS. This model exhibits good performance and can help clinicians make decisions and optimize the use of healthcare resources.

In order to realize the effective prevention and control of coal dust, the magnetic-electric coupling spray dust reduction technology is proposed. First, by measuring the surface tension and contact angle of magnetized water under different magnetization intensities and magnetization times, its wetting and atomization properties are analyzed. Secondly, the magnetized water was magnetized with optimal parameters to increase the applied electric field to explore the effects of electrode voltage, electrode ring parameters, and electrode spacing on the charging characteristics and atomization performance of magneto-electrically coupled water. Then, the dust reduction effects of ordinary water, magnetized water and magneto-electrically coupled water were compared by the self-built dust removal experimental platform. Finally, COMSOL software is used to simulate the changes of collision patterns between the above three liquids and coal dust particles. The experimental results show that: the best dust reduction parameters of magnetized water solution are magnetization intensity of 350 mT and magnetization time of 30 min; the best parameters of magneto-electrically coupled water are electrode voltage of 9 kV, electrode ring parameter of 8 cm and electrode spacing of 3.5 cm; the dust reduction efficiency of magneto-electrically coupled solution is higher than that of other two kinds of liquids, and the dust capturing efficiency of magneto-electrically coupled spray is increased by 38.84% compared with that of ordinary water at the time of total dust, and the dust reduction efficiency reaches 91.2%; the dust capture efficiency of the magneto-electrically coupled spray is 38.59% higher than that of ordinary water in respirable dust, and the dust reduction efficiency reaches 82.3%. The droplets are more easily adhered to the surface of coal dust particles under the three working conditions of ordinary water, magnetized water and magneto-electrically coupled solution.

Abstract Tumor ecosystem shapes cancer biology and potentially influence the response to immunotherapy, but there is a lack of direct clinical evidence. In this study, we utilized EcoTyper and publicly available scRNA-Seq cohorts from ICI-treated patients. We found a ecosystem subtype (ecotype) was linked to improved responses to immunotherapy. Then, a novel immunotherapy-responsive ecotype signature (IRE.Sig) was established and validated through the analysis of pan-cancer data. Utilizing IRE.Sig, machine learning models successfully predicted ICI responses in both validation and testing cohorts, achieving area under the curve (AUC) values of 0.72 and 0.71, respectively. Furthermore, using 5 CRISPR screening cohorts, we identified several potential drugs that may augment the efficacy of ICI. We also elucidated the candidate cellular biomarkers of response to the combined treatment of pembrolizumab plus eribulin in breast cancer. This signature has the potential to serve as a valuable tool for patients in selecting appropriate immunotherapy treatments.

Abstract Background Algae play important roles in urban river ecosystems and are the cornerstones of most water quality monitoring programs. Thus, a better understanding of algal community dynamics is needed to support sustainable management of water resources in urban rivers. Results In this study, we quantified the seasonal variations in planktonic and periphytic algal community structure in the highly urban Fenhe River and identified environmental factors affecting algal community structure and diversity. We monitored planktonic (drifting) and periphytic (attached) algal communities in the Taiyuan section of the Fenhe River over one year. The results indicated that Cyanophyta was the dominant phylum in both communities, followed by Bacillariophyta and Chlorophyta. Significant differences were observed in the composition of the planktonic and periphytic algal communities. In particular, the periphytic algal community was more diverse than the planktonic community. Water temperature and pH were the main environmental factors affecting planktonic and periphytic algal community structure, respectively, while nutrients were the most significant factor affecting planktonic and periphytic algal diversity. Ecological modeling indicated that the variations in the algal communities of the Fenhe River are mainly driven by stochastic processes. A co-occurrence network developed for the communities displayed positive interactions between the planktonic and periphytic algae. Conclusions These findings deepen our understanding of the seasonal interaction between planktonic and periphytic algae and the driving factors affecting community structure in the Fenhe River. They also provide a theoretical basis for the managing and protecting water resources in urban river ecosystems.

In response to the rapid growth of future business and data traffic, the widespread deployment of small base stations (BSs) in 5G networks has emerged as a promising solution, albeit intensifying the network’s energy consumption. Additionally, traditional BSs lack adaptive adjustment of parameter information, posing challenges in delivering satisfactory quality of service (QoS), particularly in the context of highly uneven business distribution. Reducing energy consumption while ensuring that QoS represents a critical challenge. To address this issue, this paper first comprehensively considers the interests of both supply and demand, proposing a service utility measurement method in communication networks to achieve a balance between energy consumption and QoS. Furthermore, this paper integrates cell zooming and sleeping strategies for small BSs, designing a dynamic game algorithm aimed at optimizing service utility in a two-tier heterogeneous network. Through ten distinct scenario simulations, our proposed algorithm demonstrates significant enhancements in service utility while achieving near-optimal optimization results more expeditiously compared to the genetic algorithm (GA).

The dense deployment of Femto Base Stations (FBS) assisting Macro Base Stations (MBS) in a Heterogeneous Network (HetNet) resolves the coverage issue of 5G signal transmission. However, the imprudent layout of FBSs results in extensive energy consumption and increased signal interference among base stations. Regulating the transmission power of each base station in the HetNets through the main controller or MBS is essential to maximize the power efficiency of the entire HetNets while adhering to the constraints of basic signal throughput and fairness. To address this challenge, this paper proposes an Adaptive Acceleration Particle Swarm Optimization (AA-PSO) algorithm. This algorithm dynamically determines the inertia weight based on each particle’s optimal position and the global optimal position, and introduces the concept of time-varying parameters to control the learning rate, thus managing the search range and convergence speed of the particle swarm. The results demonstrate that the AA-PSO algorithm can efficiently determine the optimal transmission power of each base station in the HetNets, reduce interference between MBS and FBSs, as well as among FBSs, and ultimately improve the service efficacy of the entire network.

PurposeInvestigating the diagnosis and treatment of bilateral Chylothorax after neck lymph node dissection for thyroid cancer.MethodsThe clinical data of a patient with bilateral chylothorax after neck lymph node dissection for thyroid cancer were retrospectively analyzed, and the relevant literature was reviewed.ResultsThe patient underwent a total thyroidectomy and left neck lymph node dissection, with no evidence of lymph fluid leakage observed during the operation. The patient experienced chest tightness, shortness of breath, dyspnea, and decreased lung auscultation breath sounds on the 7th day after the surgery. The chest X-ray examination revealed the presence of bilateral pleural effusion. Under ultrasound guidance, bilateral thoracic closed drainage tube was implanted, and a small sample of the milky white fluid was tested for chylothorax, yielded positive results. The patient is diagnosed with bilateral chylothorax. After received conservative treatment, the patient’s drainage flow gradually decreased. Subsequent review of a chest X-ray showed no signs of chest hydrops, and as a result, the thoracic drainage tube was removed. The patient eventually recovered and was subsequently discharged.ConclusionBilateral chylothorax is a rare complication following neck lymph node dissection for thyroid cancer. It is deemed safe and effective to administer active conservative treatment upon early detection.

The ladle shroud is a vital component in the continuous casting process of steelmaking as it supports the production of a wide range of specialty steels. However, it is plagued by a persistent issue of clogging, which not only diminishes the lifetime of the Alumina-Carbon ladle shroud but also severely disrupts the smooth operation of the continuous casting process. Utilizing a numerical simulation technique, the research adopted the method of particle-liquid two-phases coupling, to probe into the clogging mechanism in the ladle shroud from behavior of heat transfer, flow and inclusions. The study indicated that the temperature distribution and flow behavior have a positive effect on the formation of clogging, especially the inclusions. Various factors synergistically contribute on the inner wall, promoting severe clogging at the outlet of the ladle shroud. Finally, a simulation-based clogging mechanism is concluded coupling above factors.

The removal of nitrogen from farmland drainage is challenging due to the typically low carbon-to-nitrogen (C/N) ratio. In this study, an algal-bacterial symbiosis system was developed to treat low C/N farmland drainage. The investigation focused on the nutrient removal rates, microbial growth characteristics, extracellular polymeric substances (EPS) content, and microbial community species composition under varied disturbance frequencies and light conditions (intensity and duration). Results demonstrated that the optimal operating conditions were three disturbances per 24 h, a light intensity of 20,000 lux, and a 16-hour lighting duration. Under these conditions, the average removal rates of soluble chemical oxygen demand, total nitrogen, total phosphorus, nitrate nitrogen, and ammonia nitrogen reached 45.1 %, 73.3 %, 98.1 %, 63.1 %, and 97.3 %, respectively. Compared to continuous disturbance, intermittent disturbance reduced energy consumption by over 90 % and promoted higher biomass accumulation, with an average dry weight of 508.7 mg L−1 and chlorophyll-a concentration of 521.0 μg L−1. Meanwhile, a robust microbial community and a balanced bacterial-to-algal gene copy ratio (exceeding 25:1) were critical for nutrient removal. The optimized system facilitated symbiote secretion of bound polysaccharides (45.2 μg L−1, double that of other reactors), promoting the formation of robust biofilms and enhancing nutrient removal. This work provides a technical reference for improving nutrient removal in low C/N wastewater treatment processes.

ABSTRACTThis study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12–46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Abstract Background The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It’s unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. Methods This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. Results In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018–2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020–2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. Conclusion Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

Abstract The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy. Graphical Abstract

Abstract Background The administration of tranexamic acid (TXA) during spinal surgery has been shown to reduce blood loss. However, the efficacy and safety of intravenous TXA (ivTXA) and topical TXA (tTXA) are poorly documented. The present meta-analysis aimed to compare the efficacy and safety of ivTXA and tTXA administration in spinal surgery. Methods Potentially relevant academic articles were identified from PubMed, Ovid, Cochrane Library, CNKI database, and Wanfang Data from the date of inception until March 1, 2024. Randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) were included in our meta-analysis if they compared the efficacy and safety of ivTXA versus tTXA administration during spinal surgery. Secondary sources were identified from the references of the included literature. The meta-analysis was performed in accordance with the guidelines of the Cochrane Reviewer’s Handbook and the PRISMA statement. Data were summarized using RevMan 5.3 software from Denmark. Results Four RCTs and one non-RCT met our inclusion criteria. The pooled outcomes demonstrated that ivTXA groups compared with tTXA groups had significantly less amount of total blood loss [weighted mean difference (WMD)=-159.55, 95% CI (-181.91,-137.19), P

Abstract In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin–eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia–reperfusion injury.

Abstract Thermally stable full-length scorpion toxin peptides and partially degraded peptides with complete disulfide bond pairing are valuable natural peptide resources in traditional Chinese scorpion medicinal material. However, their pharmacological activities are largely unknown. This study discovered BmKcug1a-P1, a novel N-terminal degraded peptide, in this medicinal material. BmKcug1a-P1 inhibited hKv1.2 and hKv1.3 potassium channels with IC50 values of 2.12 ± 0.27 μM and 1.54 ± 0.28 μM, respectively. To investigate the influence of N-terminal amino acid loss on the potassium channel inhibiting activities, three analogs (i.e., full-length BmKcug1a, BmKcug1a-P1-D2 and BmKcug1a-P1-D4) of BmKcug1a-P1 were prepared, and their potassium channel inhibiting activities on hKv1.3 channel were verified by whole-cell patch clamp technique. Interestingly, the potassium channel inhibiting activity of full-length BmKcug1a on the hKv1.3 channel was significantly improved compared to its N-terminal degraded form (BmKcug1a-P1), while the activities of two truncated analogs (i.e., BmKcug1a-P1-D2 and BmKcug1a-P1-D4) were similar to that of BmKcug1a-P1. Extensive alanine-scanning experiments identified the bonding interface (including two key functional residues, Asn30 and Arg34) of BmKcug1a-P1. Structural and functional dissection further elucidated whether N-terminal residues of the peptide are located at the bonding interface is important in determining whether the N-terminus significantly influences the potassium channel inhibiting activity of the peptide. Altogether, this research identified a novel N-terminal degraded active peptide, BmKcug1a-P1, from traditional Chinese scorpion medicinal material and elucidated how the N-terminus of peptides influences their potassium channel inhibiting activity, contributing to the functional identification and molecular truncation optimization of full-length and degraded peptides from traditional Chinese scorpion medicinal material Buthus martensii Karsch.

Abstract Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, bla CTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.

Abstract Background The objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC). Methods Utilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission. Results During the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60–0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34–0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33–0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15–0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P

Al–Zn–Mg–Cu alloys have remarkable plasticity and aging-hardening potential, while natural aging during storage and transportation dramatically increases the strength of the alloys and deteriorates the formability by generating massive high-density nano-scaled -clusters. In this study, a combination of pre-aging and regression heat treatment was employed to improve the negative effects of natural aging via regulating the distribution of precipitates and reducing the dissolving ratio. Atomic probe tomography and transmission electron microscope observations were mainly carried out to reveal the mechanism of microstructure evolution caused by heat treatments. The results reveal that the distributions of precipitate density and size vary with different pre-aging time, resulting in the differences in dissolving critical sizes and dissolving ratios of precipitates during regression heat treatments. For the limited pre-aging time, the dramatic dissolution of nano-scale clusters caused the surge of solute concentration in the matrix after regression heat treatments, resulting in considerable secondary precipitation of clusters during the subsequent natural aging process. With the increase of pre-aging time, the size and density of precipitates gradually increased, which reduced the dissolving ratio of precipitates during regression heat treatments. However, as the dissolving ratio declined from around 97.5 % (pre-aging for 0 h) to approx. 69.2 % (pre-aging for 18 h), the solute concentration in the matrix was lower than the secondary precipitation level of clusters, thus suppressing natural aging. Overall, this work provides a novel strategy to control the nature-aging behavior of Al–Zn–Mg–Cu alloys. Meanwhile, the correlation between microstructure evolution and mechanical properties under different heat treatments was systematically discussed.

Abstract The inadequate stability of organic–inorganic hybrid perovskites remains a significant barrier to their widespread commercial application in optoelectronic devices. Aging phenomena profoundly affect the optoelectronic performance of perovskite-based devices. In addition to enhancing perovskite stability, the real-time detection of aging status, aimed at monitoring the aging progression, holds paramount importance for both fundamental research and the commercialization of organic–inorganic hybrid perovskites. In this study, the aging status of perovskite was real-time investigated by using terahertz time-domain spectroscopy. Our analysis consistently revealed a gradual decline in the intensity of the absorption peak at 0.968 THz with increasing perovskite aging. Furthermore, a systematic discussion was conducted on the variations in intensity and position of the terahertz absorption peaks as the perovskite aged. These findings facilitate the real-time assessment of perovskite aging, providing a promising method to expedite the commercialization of perovskite-based optoelectronic devices. Graphical Abstract

Abstract It is essential to elucidate the mechanical mechanism of water injection and large-diameter drilling pressure relief measures on coal rock deformation and failure. This helps coal mines adopt more precise and effective dynamic disaster prevention and control measures. To obtain the mechanical response mechanism and energy evolution characteristics of saturated coal with a single pre-existing hole, uniaxial compression tests was carried out, and the deformation and failure process of coal samples were monitored by high-speed camera and acoustic emission monitoring systems. It is found that water saturation, single pre-existing hole measures, and their coupling effect resulted in a deterioration in the coal sample's strength by approximately 23.49%, 9.47%, and 47.95% respectively. The final failure mode of coal samples with different measures is shear failure. The law of fracture development and expansion and energy accumulation and release in different coal samples is roughly the same, the speed of energy accumulation and release in different stages is different. Water saturation and single pre-existing hole measures can affect the impact risk of coal samples, and water saturation can significantly reduce the impact tendency of coal samples, and reduce the impact energy index of complete coal samples by 56.59%. The impact tendency index of natural coal sample is slightly increased by single pre-existing hole measure, and the impact energy index of intact coal sample is reduced by 46.78% by the coupling of the two measures. These findings can provide technical support for coal mine power disaster prevention and control.

Abstract. The advent of chimeric antigen receptor (CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological malignancies. However, their success in treating solid tumors has been limited. CAR-natural killer (NK) cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex (MHC), which means they are more likely to become an "off-the-shelf" product. Moreover, they can kill cancer cells via CAR-dependent/independent pathways and have limited toxicity. Macrophages are the most malleable immune cells in the body. These cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments (TMEs). Importantly, CAR-macrophages (CAR-Ms) have recently yielded exciting preclinical results in several solid tumors. Nevertheless, CAR-T, CAR-NK, and CAR-M all have their own advantages and limitations. In this review, we systematically discuss the current status, progress, and the major hurdles of CAR-T cells, CAR-NK cells, and CAR-M as they relate to five aspects: CAR structure, therapeutic mechanisms, the latest research progress, current challenges and solutions, and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.

Abstract Objective This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. Methods The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain’s sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. Results Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. Conclusion This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as bla NDM−1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.

Abstract Nucleotides, such as uridine 5′‐monophosphate (5′‐UMP) and cytidine 5′‐monophosphate (5′‐CMP), are heavily demanded as food additives, dietary supplements, and medicinal intermediates. Although enzymatic phosphorylation is an effective approach to producing these nucleosides, its practical application is challenging due to the need for the expensive enzymes and coenzyme guanosine‐5′‐triphosphate (GTP). Here we prepared biocompatible calcium‐based nanoflowers incorporated with cascade enzymes, uridine‐cytidine kinase (UCK) and acetate kinase (ACK), for the production of nucleotides. The spatial distribution of these enzymes was optimized to maximize their catalytic performances. The most active nanoflowers (Ca3(PO4)2& ACK)& UCK that display the rate‐limiting enzyme UCK on the outer layer were used in a packed‐bed reactor for continuous synthesis of 5′‐UMP and 5′‐CMP. The catalytic performance of the catalyst retained over 80% within 10 h, showing good operational stability.

The treatment of tendon/ligament-to-bone injury is a long-standing research challenge in orthopedics and bone tissue engineering. Orderly healing of the fibrocartilage layer and mineralized bone layer is crucial for treating tendon-bone interface injuries. We designed a three-dimensional printed porous titanium scaffold composite system with thermosensitive collagen hydrogel loaded with transforming growth factor β3 (TGF-β3), formulated for the sustained slow release of TGF-β3 at a constant rate. In vitro, the composite system exhibited good biocompatibility and was beneficial for the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs), which showed high growth activity. Moreover, the composite system promoted the differentiation of BMSCs via osteogenesis and chondrogenesis. In vivo, the composite system provided active substances at the injured site, promoting the repair of the fibrocartilage layer and of the mineralized bone layer at the interface between the ligament and bone. Micro-CT results demonstrated that the complex promotes the osseointegration of titanium scaffolds in bone defects. Hard tissue sections showed that the new bone, ligament, and the titanium alloy scaffold system formed a closely integrated whole; the composite system provided suitable attachment points for ligament growth. Additionally, the biomechanical strength of the tendon interface improved to some extent. Our results indicate that the composite system has potential as a bioactive implant interface for repairing ligament and bone injuries.

Over 60% of breast cancer cases are diagnosed with estrogen-receptor (ER) positive. Tamoxifen (TAM), a commonly employed medication for ER-positive breast cancer, often yields suboptimal therapeutic outcomes due to the emergence of TAM resistance, leading to the recurrence and a poor prognosis. The copper transporter, solute carrier family 31 member 1 (SLC31A1), has been associated with tumor aggressiveness and unfavorable outcomes in various types of tumors. In our current study, we found high expression of SLC31A1 that predicted poor survival in patients with breast cancer. Significantly, ER-positive breast cancer tissues in patients with recurrence post-TAM treatment exhibited considerably stronger SLC31A1 expression levels. In vitro experiments verified that TAM-resistant ER-positive breast cancer cell lines expressed notably higher SLC31A1 levels compared to the parental cell lines. Of great significance, SLC31A1 depletion notably rescued TAM sensitivity in chemoresistant ER-positive breast cancer cells, as demonstrated by the attenuated cell proliferative and invasive capabilities. Conversely, promoting SLC31A1 significantly facilitated the proliferation and invasion of wild-type breast cancer cells. Subsequently, we detected reduced copper levels in TAM-resistant breast cancer cells with SLC31A1 depletion. Mechanistically, we observed that in chemoresistant breast cancer cell lines, SLC31A1 knockdown resulted in a substantial decrease in the expression of carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme of fatty acid oxidation (FAO). RNA-Seq analysis indicated that FAO might be implicated in SLC31A1-mediated breast cancer progression. CPT1A was also overexpressed in TAM-resistant breast cancer cells, accompanied by enhanced FAO rates and ATP levels. Suppressing CPT1A significantly enhanced the chemosensitivity of TAM-resistant breast cancer cells in response to TAM treatments. Intriguingly, copper exposure dose-dependently increased CPT1A expression in chemoresistant breast cancer cells, but this could be abolished upon SLC31A1 knockdown, along with enhanced apoptosis, which elucidated that copper uptake contributed to CPT1A expression. Furthermore, SLC31A1 overexpression significantly augmented CPT1A expression in parental breast cancer cells, accompanied by facilitated copper levels, FAO rates, and ATP levels, while being notably diminished upon CPT1A suppression. Finally, our in vivo studies confirmed that SLC31A1 deficiency re-sensitized TAM-resistant breast cancer cells to TAM treatment and abolished tumor growth. Collectively, all our studies demonstrated that SLC31A1/copper suppression could enhance TAM responses for chemoresistant ER-positive breast cancer cells through constraining the CPT1A-mediated FAO process.

Abstract BackgroundOccupational noise–induced deafness (ONID) has replaced occupational poisoning as the second most common occupational disease in China since 2015. However, there is a limited number of articles on epidemiological characteristics of legally diagnosed ONID. ObjectiveWe conducted a comprehensive analysis of the epidemiological and spatiotemporal characteristics of ONID in Guangdong Province from 2006 to 2022, with the aim of providing a scientific foundation for policy formulation and health resource allocation. MethodsSurveillance data of ONID cases in Guangdong Province from 2006 to 2022 were obtained from the “Occupational Diseases and Health Hazard Factors Monitoring Information System.” Joinpoint regression analysis was applied to assess the long-term trends in cases of ONID from 2006 to 2022. Global spatial autocorrelation analysis was performed to measure the overall degree of similarity of the attribute values of spatially adjacent or neighboring regional units. The local indicators of spatial autocorrelation (LISA) plots were then used to identify the local clusters of ONID in Guangdong. ResultsThere were 3761 ONID cases in Guangdong Province from 2006 to 2022, showing a significantly increased trend in cases across the entire study period (average annual percentage change 21.9, 95% CI 18.7-35.1). The Moran’s I values for the period of 2006 to 2022 ranged from 0.202 to 0.649 (all P ConclusionsSignificant spatiotemporal patterns of ONID in Guangdong Province from 2006 to 2022 were identified, characterized by a dramatic increase followed by stabilization in case numbers. ONID predominantly occur in manufacturing industries, domestically funded enterprises, among males, individuals aged 40‐49 years, and those with 5+ years of occupational noise exposure. Spatial analysis demonstrated significant clustering in the Pearl River Delta region, with consistent positive spatial autocorrelation across years. These results could help prioritize the allocation of resources for targeted prevention and control measures for ONID.

ABSTRACT Biodiversity and ecosystem multifunctionality are currently hot topics in ecological research. However, little is known about the role of multitrophic diversity in regulating various ecosystem functions, which limits our ability to predict the impact of biodiversity loss on human well‐being and ecosystem multifunctionality. In this study, multitrophic diversity was divided into three categories: plant, animal, and microbial communities (i.e., plant diversity, rodent diversity, and bacterial and fungal diversity). Also, 15 ecosystem functions were divided into four categories—water conservation, soil fertility, nutrient cycling and transformation, and community production—to evaluate the significance of biotic and abiotic variables in maintaining ecosystem multifunctionality. Results indicated that species diversity at multiple trophic levels had a greater positive impact on ecosystem multifunctionality than species diversity at a single trophic level. Notably, the specific nature of this relationship depended on the niche breadths of plants, indicating that plants played a key role in linking above and belowground trophic levels. Abiotic factors such as altitude and pH directly acted on ecosystem multifunctionality and could explain changes in ecosystem functions. Overall, our study offers valuable insights into the critical role of multitrophic species diversity in preserving ecosystem multifunctionality within alpine grassland communities, as well as strong support for the importance of biodiversity protection.

Interleukin-15 (IL-15) is a crucial cytokine involved in immune system regulation, which is produced by various cell types, including dendritic cells, monocytes, and macrophages. IL-15 plays a key role in the proliferation and activation of natural killer (NK) cells, CD8+ T cells, and memory CD8+ T cells, supporting their survival and enhancing their effector functions. Although IL-15 homologues in fish have been identified, their functions remain poorly understood. In this study, we cloned and investigated the bioactivities of an IL-15 homologue, referred to as IL-15 like (CcIL-15L), in common carp (Cyprinus carpio L.). An expression pattern analysis revealed that CcIL-15L was constitutively expressed in all examined tissues of healthy common carp, with the highest expression level observed in the intestine. Additionally, CcIL-15L expression was significantly up-regulated in the head kidney, spleen, gills, and intestine following Aeromonas hydrophila infection. In vitro, the recombinant protein CcIL-15L can significantly up-regulated the gene expression levels of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, and TNF-α) and NK cell activation (perforin and Eomesa). We constructed a 3×FLAG eukaryotic expression vector and successfully expressed it in common carp by intramuscular injection. Additionally, the heterologous CcIL-15L protein was successfully overexpressed in vivo, and immune-related genes including CD4-1, CD8β2, TNF-α, and IgM showed significant induction in the head kidney and spleen. Furthermore, CcIL-15L overexpression reduced the bacterial loads after 24 h post-A. hydrophila infection in the liver, spleen, and kidney. Phagocytic and chemotaxis assays showed that rCcIL-15L could promoted the phagocytosis and chemotactic abilities of common carp HKLs. Our study provides a new perspective on the role for CcIL-15L in immunological functions in common carp.

Dysregulated calcium (Ca2+) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca2+ influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both in vitro and in vivo. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.

Objective To analyze the geographic variation in characteristics and treatment processes of patients with acute ischemic stroke (AIS) in coastal, island, and inland regions. Methods We conducted a retrospective, cross-sectional analysis of data from patients with AIS in southeastern China. We collected demographic and clinical information, including the time from stroke onset to treatment for those receiving reperfusion therapy, using a time-tracking table. Results Among 8069 patients with AIS, 26.6% received reperfusion therapy, with a higher proportion undergoing endovascular therapy in maritime hospitals than in inland hospitals (14.2% vs. 6.7%). Maritime hospitals had a higher prevalence of atrial fibrillation (15.1% vs. 11.9%) and cardioembolism (17.2% vs. 13.6%) than inland hospitals. Patients in maritime hospitals had shorter in-hospital processing times than those in inland hospitals (39 vs. 46 minutes). Island hospitals showed different patterns, with a shorter time from stroke onset to emergency room arrival (80 vs. 120 minutes) but a longer in-hospital process time (51 vs. 36 minutes), than coastline hospitals. Conclusions Our study suggests geographic variation in AIS characteristics and treatment processes across southeastern China, emphasizing the need for region-specific strategies. These findings are essential for tailoring public health policies and guidelines to improve stroke outcomes in various regions.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance mutations. Therefore, finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system (UPS) has emerged as a focus. The UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological processes. In recent years, the study of UPS in hematological malignant tumors has resulted in effective treatments, such as bortezomib in the treatment of multiple myeloma and mantle cell lymphoma. In CML, the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL, interfering with CML-related signaling pathways, and negatively or positively affecting leukemia stem cells. Some of these molecules may help overcome TKI resistance and treat CML. In this review, the mechanism of TKI resistance is briefly described, the components of UPS are introduced, existing studies on UPS participating in TKI resistance are listed, and UPS as the therapeutic target and strategies are discussed.