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The article considers the state of the world oil market at the present stage andassessed the prospects for its furtherdevelopment. A complex system of statistical indicators of the world oil market was proposed on the basis of generalizationof international experience and taking intoaccount the Russian statistical practice. Amultidimensional classification of the main oil-producing countries was done in orderto identify homogeneous groups and determine the place of Russia in this market.Obtained projections for key indicators ofthe world oil market in the medium term.

Abstract Background Preoperative smoking cessation may reduce postoperative complications in patients with lung cancer. However, the optimal duration of short-term preoperative smoking cessation remains unclear. Methods Three databases, PubMed, Embase, and the Cochrane Library, were searched for studies published up to April 5, 2024. The Newcastle–Ottawa scale was used to assess the risk of bias. The included studies compared the incidence of postoperative complications between patients with different preoperative smoking cessation times and those with persistent preoperative smoking. A meta-analysis of postoperative complications and events such as pneumonia was performed in patients with lung cancer. Results Fourteen studies met the inclusion criteria and included a total of 50,741 patients who had undergone pulmonary resection. The meta-analysis showed that preoperative smoking cessation of > 2 weeks and 1 month was effective in reducing the incidence of postoperative complications (OR 0.72; 95% CI 0.63–0.83; P 1 month is effective in reducing complications and pneumonia after pulmonary resection in patients with lung cancer, especially as video-assisted thoracoscopic surgery (VATS) and robotic-assisted surgery become more common.

Abstract Chinese hamster ovary (CHO) cells are common mammalian cell lines for expressing recombinant proteins, yet the expression level of recombinant proteins is still hindered. Vector optimization and cell line modification are the key factors to improve the expression of recombinant proteins. In this study, the vector was optimized by adding the regulatory elements Kozak and Leader to the upstream of target gene to detect the transient and stable expression of recombinant proteins. Results indicated that the expression level of target proteins with the addition of regulatory elements was significantly increased compared with the control group. In addition, the inhibition of apoptotic pathway has great potential to increase recombinant protein production, and Apaf1 protein dependent on the mitochondrial apoptosis pathway plays an important role in this respect. The knockout of apoptotic gene Apaf1 in CHO cells can also increase recombinant protein production. Therefore, the vector was optimized by adding regulatory elements, and the cell line was modified by using CRISPR/Cas9 technology to establish a novel CHO cell expression system, which remarkably improved the expression level of recombinant proteins and laid the foundation for the large-scale production of recombinant proteins.

Abstract Rational design of bimetallic alloy is an effective way to improve the electrocatalytic activity and stability of Mo-based cathode for ampere-level hydrogen evolution. However, it is still critical to realise desirable syntheses due to the wide reduction potentials between different metal elements and uncontrollable nucleation processes. Herein, we propose a rapid Joule heating method to effectively load RuMo alloy onto MoOx matrix. As-prepared catalyst exhibits excellent stability (2000 h @ 1000 mA cm−2) and ultralow overpotential (9 mV, 18 mV and 15 mV in 1 M KOH, 1 M PBS, 0.5 M H2SO4 solution, respectively) at 10 mA cm−2. Based on first-principle simulations and operando measurements, the impressive electrocatalytic stability and activity are investigated. And the role of rapid Joule heating method is highlighted and discussed in details. This study showcases rapid Joule heating as a feasible strategy to construct highly efficient alloy-based electrocatalysts.

Acoustic fish driving technology, as an auxiliary fish passage measure and a non-physical barrier, is based on the use of sound signals to prevent or regulate fish behavior. The purpose of these techniques is to guide the fish away from dangerous areas, such as the water inlets of hydroelectric power stations, spillways, and ship locks, allowing them to easily locate the entrance to the fishway, which would help improve fish passage efficiency. Studying the negative phonotaxis behavior of fish is vital for establishing non-physical barriers using acoustic characteristics. However, there has been little research on verifying the effectiveness of acoustic fish deterrence technology in field environments. Therefore, this study used alternating sound playback to conduct negative phonotaxis experiments on grass carp (Ctenopharyngodon idellus) juveniles to explore their behavioral responses to different sounds. The experimental tank (3.6 m×1.1 m×1.0 m) was created in the waters of Xialao Creek in Yichang City, Hubei Province, with an average water depth of 0.5 m and an average flow rate of 0.06 m/s. The experiment used one single-frequency sound (1 000 Hz) and five complex sounds (fish swimming, engine, short-nosed crocodile call, pile driving, and yacht sounds), with a sound pressure level of (117.69±2.77) dB re 1 μPa. The effectiveness of acoustic fish-repellent technology has been proven, but there are only a few applications in practical engineering. On the one hand, the theoretical knowledge is not comprehensive, and on the other hand, there is a gap between theoretical research and practical engineering. Moreover, there are differences in proton movement (vibration) modes between indoor and natural environments. Compared with fish in an indoor environment, fish in natural waters tend to receive sound signals by proton movement rather than sound pressure. At the same time, the distribution of the sound field in natural and indoor environments also differs; thus, field experiments are necessary for the advancement of acoustic fish-repellent technology. Globally, studies on the negative phonotaxis of fish have mainly been conducted in vitro. Detailed studies using natural open water conditions are insufficient, and further field verification experiments are needed. Therefore, this study conducted experiments in natural open water, compared the sound field changes in the natural and indoor environments, and studied negative phonotaxis behavior by observing reaction time, initial reaction time, average reaction time, phonotaxis speed, movement time ratio, and other indicators. The results showed that when the complex sounds were played, the reaction times, tone trend speed and movement time ratio of grass carp were significantly higher than that of single tone and control group (P < 0.001), and the initial reaction time and average reaction time of grass carp were significantly lower than that of single tone and control group (P < 0.001). Among the complex sounds, the grass carp stimulated by the yacht sound had the largest response times and speed, while the grass carp stimulated by the fish swimming sound had the smallest response times and speed. In the complex sound, the first response time of grass carp stimulated by yacht sound was the shortest, which was (23.40±5.13) s. The first response time of grass carp stimulated by engine sound was (146.00±7.82) s, which was significantly lower than that of other complex sounds (P < 0.05). The average response time of grass carp stimulated by the sound of yacht and pile was (26.52±3.01) s and (28.76±4.07) s, respectively. The average response time of grass carp stimulated by fish swimming sound was (64.76±17.82) s. In the complex sound, the motion time ratio of grass carp stimulated by fish swimming sound was the highest, which was (98.47±0.48)%. The motion time ratio of grass carp stimulated by engine sound was (94.58±0.54)%. There were no significant differences in reaction times, initial reaction time, average reaction time and exercise time ratio between grass carp and control group when playing single frequency tone (P > 0.05). The experimental results indicated that the five complex sounds used in this study (fish swimming, engine, short-nosed crocodile call, pile driving, and yacht sounds) all had a deterrent effect on grass carp juveniles. This study not only enriches current knowledge of the negative phonotaxis behavior of fish but also provides a scientific basis for the design and optimization of sound-based fish deterrent facilities in practical engineering.

Objective To understand the clinical characteristics and microecological status of lower genital tract in females with genital herpes in gynecological clinic in order to standardize the treatment of genital herpes. Methods A total of 27 women diagnosed with genital herpes were enrolled from the gynecological clinic of Beijing Obstetrics and Gynecology Hospital, Capital Medical University. The clinical data and vaginal microecology of participants were analyzed. Results All patients presented with various degree of external genital itching, pain, burning pain, sting pain, etc. Gynecological examination showed typical external genital herpes and/or irregular small ulcers. One case presented with cervical herpes-like changes. Abnormal vaginal microecology was observed in 88.89% of the patients (24/27), including 8 cases of decreased function of flora, 2 cases of bacterial vaginosis, 6 cases of vulvovaginal candidiasis, 7 cases of abnormal flora, and 1 case of mixed infections. The pH of vaginal secretions was higher, evidenced by 22 cases (22/27, 81.48%) with pH >4.5. Conclusions The clinical manifestations of female genital herpes vary and are often accompanied by vaginal dysbiosis. In clinic, it is recommended to conduct vaginal microbiota examination and personalize targeted treatment for all women with suspected genital herpes.

The complex tectonic stress in the Shunbei area of the central Tarim Basin results in varied patterns of multilayered fractures. When drilling into the Silurian fracture zone and the formation pressure is lower than the drilling fluid column pressure, leakage easily occurs. To ensure efficient drilling, it is crucial to conduct an analysis of Silurian fracture characteristics and stress field disturbances to guide well design. Through enhanced interpretation and spatial analysis of Silurian faults, a comprehensive analysis of fractures was conducted in conjunction with the fault growth index. The overall characteristics of fractures in the study area included steeply dipping strike-slip faults and overlying en echelon normal faults with layered deformation. The Silurian fracture patterns primarily consist of echelon negative flower-like normal fault combinations, reflecting activity from late Caledonian to early Hercynian. The principal stress direction of the Silurian is 54° NE based on dipole array acoustic logging data from well SHZ1. By integrating three-dimensional seismic data interpretation with geological modeling and iterative boundary element numerical simulations, the current spatial distribution of stress fields, including maximum, minimum, and intermediate principal stresses, was established. The results of the stress field simulation were compared with interpretations derived from actual logging data. Due to the influence of fault occurrence and spacing, the width of stress disturbance zones varies on the plane, and stress disturbances above and below the fault plates show an asymmetric distribution. Through spatial sculpting of Silurian fractures and analysis of stress disturbances, optimal well locations and trajectories were selected to avoid areas with high fracture intensity, large dip angles, concentrated stress zones, strong energy anomaly fractures, and developed crack zones. The comprehensive analysis of Silurian fractures and stress field disturbance ensures efficient drilling and mitigates risks of significant Silurian leakage during well optimization.

Abstract Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co3+ and Co2+ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2 nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

Abstract Background Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. Methods A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. Results A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. Conclusion The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Abstract This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2–Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2–Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2–Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

The primary function of plant fibers in reconstituted tobacco is to enhance the physical strength, and it can quite modify their physical properties. This study demonstrated the effect of various plant fibers and their beating degrees on the physical properties of reconstituted tobacco. Tensile index, burst index, uniformity, tensile stiffness orientation, and thermal conductivity coefficient were examined. The result revealed that the mechanical properties of reconstituted tobacco varied according to the type and beating degree of the fibers. The mechanical properties of softwood, cotton, and bast fibers showed an initial increase followed by a decrease with increasing beating degree, while bamboo fiber showed a continuous improvement in mechanical properties proportional to the beating degree. Conversely, hardwood fiber displayed an inverse relationship with its beating degree. Under identical beating conditions, reconstituted tobacco containing softwood fibers showed the greatest improvement in tensile properties, achieving the highest tensile strength, thermal conductivity, and specific heat capacity. In particular, when softwood fibers were beaten to 50 °SR, the physical properties of the reconstituted tobacco peaked, with longitudinal and transverse tensile indices improving by 42.48% and 12.11%, respectively. Additionally, the bursting resistance index increased by 61.93%, and the thermal conductivity coefficient increased by 5.94%.

Understanding the puff-by-puff delivery mechanisms of key components of heated tobacco products is critical to developing product designs. This study investigates the puff-by-puff release patterns of key components in Natural Smoke Cigarettes (NSCs), which are designed to deliver nicotine without combustion by reducing oxygen content, utilizing a 30-s puff interval, a 2-s puff duration, and a 55 mL puff volume to simulate realistic smoking conditions. By establishing models to analyze the variation of nicotine, glycerol, 1,2-propylene glycol (PG), and water in different functional sections of the cigarette under controlled smoking conditions. These sections include the tobacco, hollow, cooling, and filter sections, constituting the structure of NSCs. In addition, the model calculates the port-by-port release of the components in the flue gas aerosol and compares it with the measured value. The results showed that: The retention amount in the tobacco section showed a steep decline in the first three puffs, with an overall exponential decrease. The amounts in the other sections were consistent, increasing in the first two puffs and then stabilizing. The retention amount decreased linearly with each puff, with a similar pattern across sections. The release amount peaked at the fourth to fifth puffs and then stabilized. The retention amount in the tobacco section declined exponentially in the first three puffs. It peaked in the second to third puffs in other sections, then decreased with each subsequent puff. The retention amount in the tobacco section showed a significant decline in the first puff, stabilizing at around 4 mg. In other sections, it peaked at the first puff and then rapidly declined. These findings can inform the development of reduced-harm smoking products and contribute to a better understanding of the dynamics of smoke generation. Additionally, the study offers a reference for the puff-by-puff release stability of NSCs and the improvement of consumers’ sensory quality.

IntroductionThe endometrium plays a crucial role in early human pregnancy, particularly in embryo implantation, survival, and growth. However, invasion and infection by pathogens can lead to endometritis, infertility, and poor reproductive outcomes. Understanding the mechanisms of endometritis and its impact on fertility remains limited. An infection model using patient-derived endometrial epithelial gland organoids (EEGOs) was established to advance in vitro studies on endometritis and related infertility.MethodsAn EEGOs infection model was constructed and characterized from human endometrium, treating the organoids with estrogen and progesterone to observe changes in the proliferative and secretory phases. The organoids were infected with E. coli, and the release of inflammatory cytokines in the supernatant was detected using ELISA. RNA-seq was employed to analyze the differences before and after E. coli treatment, and differential gene mRNA expression was validated using real-time quantitative PCR. Additionally, the effect of E2 in alleviating inflammation was assessed through markers of receptivity (PAEP, LIF, ITGβ), proliferation (Ki67), and barrier repair (ZO-1).ResultsThe constructed human EEGOs exhibited long-term expansion capability, genetic stability, and characteristic hormonal responses, strongly expressing epithelial markers (MUC1, E-Cadherin). After E. coli infection, the expression levels of inflammatory cytokines TNF-α, IL-8, and IFN-γ increased significantly (P

Abstract Tamaricaceae comprises about 120 species and has a long evolutionary history, Tamarix Linn accounts for approximately 75% of the total species in this family. It is the most widely distributed and diverse genus in the family. They have important ecological significance for transforming deserts and improving climate conditions. However, Tamarix is the most poorly classified genera among flowering plants owing to its large variability and high susceptibility to interspecific hybridization. In this study, the complete chloroplast genomes of three Tamarix species and one draft chloroplast genome were obtained in this study. Combined with eight chloroplast genomes deposited in GenBank, complete chloroplast sequences of 12 Tamarix species were used for further analysis. There are 176 non‐SSR‐related indels and 681 non‐indel‐related SSRs in the 12 Tamarix chloroplast genomes. The mononucleotide SSRs are the most prevalent among all types of SSRs. The mVISTA results indicate high sequence similarities across the chloroplast genome, suggesting that the chloroplast genomes are highly conserved, except for sample Tamarix androssowii (ENC850343). The IR regions and the coding regions are more conserved than the single‐copy and noncoding regions. The trnF‐ndhJ, ndhC‐trnM‐CAU, ycf1, and trnL‐UAG‐ndhF regions are the most variable and have higher variability than those of the universal DNA markers. Finally, the first phylogenetic tree of Tamaricaceae was constructed which confirmed the monophyly of Tamarix in Tamaricaceae. The first phylogenetic tree of Tamarix was based on the complete chloroplast genome to date, the changes in branch length and support rate can potentially help us clarify the phylogenetic relationships of Tamarix. All the obtained genetic resources will facilitate future studies in population genetics, species identification, and conservation biology of Tamarix.

In the 2023 hurricane season, the Hurricane Analysis and Forecast System (HAFS) based Ensemble Prediction System (EPS) was being ported to the Amazon Web Service cloud. This relocation aimed to provide real-time hurricane probabilistic forecast guidance for National Hurricane Center (NHC) forecasters. The system comprises Stochastically Perturbed Physics Tendencies (SPPT), Stochastically Kinetic Energy Backscatter (SKEB), and Stochastically Perturbed PBL Humidity (SHUM). Initial and boundary conditions are derived from the National Centers for Environmental Prediction (NCEP) operational Global Ensemble Forecast System (GEFS) 21-member forecast data. The performance of HAFS-EPS for 2023 Atlantic hurricane forecasts was compared with the global GEFS, global ECMWF ensemble, and operational HAFS-A/B forecasts. This comparison highlighted the advantages of higher-resolution regional ensemble forecasts for hurricane track, intensity, Rapid Intensification (RI) probability, and various hazards, including wind, wave, and storm surge probability guidance.

IntroductionDNA methylation inhibitors (azacitidine, decitabine) have revolutionized the treatment dilemma of myelodysplastic syndromes (MDS), a group of malignant hematopoietic disorders. This study evaluates the adverse drug reactions (ADRs) following the use of DNA methylation inhibitors in the World Health Organization (WHO) VigiAccess database and compares the characteristics of ADRs between the two drugs to select the drug with the minimum individualized risk for patients.MethodsThis study employed a retrospective descriptive analysis method. We compiled ADR reports for two marketed DNA methylation inhibitors for the treatment of MDS from WHO-VigiAccess. Data collected included demographic data such as age groups, gender, and regions of global patients covered by ADR reports, as well as data on the disease systems and symptoms caused by ADRs recorded in the annual reports and reports received by WHO. By calculating the proportion of ADRs reported for each drug, we compared the similarities and differences in ADRs between the two drugs.ResultsOverall, 23,763 adverse events (AEs) related to the two DNA methylation inhibitors were reported in VigiAccess. The results showed that the top 10 most common AEs were febrile neutropenia, bone marrow suppression, neutropenia, anemia, pancytopenia, leukopenia, thrombocytopenia, bone marrow failure, agranulocytosis, and hematotoxicity. The top five common types of DNA methylation inhibitor AEs were blood and lymphatic system disorders (11,178 cases, 47.0%), cardiac organ diseases (1,488 cases, 6.3%), various congenital familial genetic diseases (49 cases, 0.2%), ear and labyrinth diseases (100, 4.2%), and endocrine system diseases (57, 2.4%).ConclusionThere is no Strong correlation between DNA methylation inhibitors and ADRs. Current comparative observational studies of these inhibitors show that there are common and specific adverse reactions in the ADR reports received by WHO for these drugs. Clinicians should improve the rational use of these drugs based on the characteristics of ADRs.

Abstract The interplay of lattice, electronic, and spin degrees of freedom at epitaxial complex oxide interfaces provides a route to tune their magnetic ground states. Unraveling the competing contributions is critical for tuning their functional properties. The relationship between magnetic ordering and magnetic anisotropy and the lattice symmetry, oxygen content, and film thickness in compressively strained LaMnO3 (LMO)/LaCrO3 (LCO) superlattices is investigated. Mn–O–Cr antiferromagnetic superexchange interactions across the heterointerface result in a net ferrimagnetic magnetic structure. Bulk magnetometry measurements reveal isotropic in‐plane magnetism for as‐grown oxygen‐deficient thin samples due to equal fractions of orthorhombic a+a‐c‐, and a‐a+c‐ twin domains. As the superlattice thickness is increased, in‐plane magnetic anisotropy emerges as the fraction of the a+a‐c‐ domain increases. On annealing in oxygen, the suppression of oxygen vacancies results in a contraction of the lattice volume, and an orthorhombic to rhombohedral transition leads to isotropic magnetism independent of the film thickness. The complex interactions are investigated using high‐resolution synchrotron diffraction and X‐ray absorption spectroscopy. These results highlight the role of the evolution of structural domains with film thickness, interfacial spin interactions, and oxygen‐vacancy‐induced structural phase transitions in tuning the magnetic properties of complex oxide heterostructures.

Abstract Class IIa histone deacetylases (Class IIa HDACs) play critical roles in regulating essential cellular metabolism and inflammatory pathways. However, dissecting the specific roles of each class IIa HDAC isoform is hindered by the pan‐inhibitory effect of current inhibitors and a lack of tools to probe their functions beyond epigenetic regulation. In this study, a novel PROTAC‐based compound B4 is developed, which selectively targets and degrades HDAC7, resulting in the effective attenuation of a specific set of proinflammatory cytokines in both lipopolysaccharide (LPS)‐stimulated macrophages and a mouse model. By employing B4 as a molecular probe, evidence is found for a previously explored role of HDAC7 that surpasses its deacetylase function, suggesting broader implications in inflammatory processes. Mechanistic investigations reveal the critical involvement of HDAC7 in the Toll‐like receptor 4 (TLR4) signaling pathway by directly interacting with the TNF receptor‐associated factor 6 and TGFβ‐activated kinase 1 (TRAF6‐TAK1) complex, thereby initiating the activation of the downstream mitogen‐activated protein kinase/nuclear factor‐κB (MAPK/NF‐κB) signaling cascade and subsequent gene transcription. This study expands the insight into HDAC7's role within intricate inflammatory networks and highlights its therapeutic potential as a novel target for anti‐inflammatory treatments.

Abstract Developing novel lead‐free ferroelectric materials is crucial for next‐generation microelectronic technologies that are energy efficient and environment friendly. However, materials discovery and property optimization are typically time‐consuming due to the limited throughput of traditional synthesis methods. In this work, we use a high‐throughput combinatorial synthesis approach to fabricate lead‐free ferroelectric superlattices and solid solutions of (Ba0.7Ca0.3)TiO3 (BCT) and Ba(Zr0.2Ti0.8)O3 (BZT) phases with continuous variation of composition and layer thickness. High‐resolution x‐ray diffraction (XRD) and analytical scanning transmission electron microscopy (STEM) demonstrate high film quality and well‐controlled compositional gradients. Ferroelectric and dielectric property measurements identify the “optimal property point” achieved at the composition of 48BZT–52BCT. Displacement vector maps reveal that ferroelectric domain sizes are tunable by varying {BCT–BZT}N superlattice geometry. This high‐throughput synthesis approach can be applied to many other material systems to expedite new materials discovery and properties optimization, allowing for the exploration of a large area of phase space within a single growth.

As the electric power market reform deepens, the strategic role of load aggregators in demand-side response becomes increasingly important. The inherent variability of distributed renewable energy generation and user demand response often leads to a mismatch between the purchased electricity and the market bid volume, resulting in punitive costs for companies. To address this issue, this study treats demand-side controllable loads as dispatchable resources and proposes a tiered pricing strategy to adjust power distribution. By establishing a Stackelberg leader-follower game model, the study promotes a mutually beneficial relationship between load aggregators and controllable load users. Through case studies, this paper examines the operational profits of load aggregators and the power adjustment behaviors of controllable load users under tiered and fixed compensation pricing schemes. The results indicate that tiered compensation pricing significantly reduces punitive costs and enhances user participation in demand response.

Abstract This study aims to enhance the safety and efficiency of port navigation by reducing ship collision accidents, minimizing environmental risks, and optimizing waterways to increase port throughput. Initially, a three-dimensional map of the port’s waterway, including data on water depth, rocks, and obstacles, is generated through laser radar scanning. Visual perception technology is adopted to process and identify the data for environmental awareness. Single Shot MultiBox Detector (SSD) is utilized to position ships and obstacles, while point cloud data create a comprehensive three-dimensional map. In order to improve the optimal navigation approach of the Rapidly-Exploring Random Tree (RRT), an artificial potential field method is employed. Additionally, the collision prediction model utilizes K-Means clustering to enhance the Faster R-CNN algorithm for predicting the paths of other ships and obstacles. The results indicate that the RRT enhanced by the artificial potential field method reduces the average path length (from 500 to 430 m), average time consumption (from 30 to 22 s), and maximum collision risk (from 15 to 8%). Moreover, the accuracy, recall rate, and F1 score of the K-Means + Faster R-CNN collision prediction model reach 92%, 88%, and 90%, respectively, outperforming other models. Overall, these findings underscore the substantial advantages of the proposed enhanced algorithm in autonomous navigation and collision prediction in port waterways.

Abstract Prolonged and over-excessive interaction with cyberspace poses a threat to people’s health and leads to the occurrence of Cyber-Syndrome, which covers not only physiological but also psychological disorders. This paper aims to create a tree-shaped gold-standard corpus that annotates the Cyber-Syndrome, clinical manifestations, and acupoints that can alleviate their symptoms or signs, designating this corpus as CS-A. In the CS-A corpus, this paper defines six entities and relations subject to annotation. There are 448 texts to annotate in total manually. After three rounds of updating the annotation guidelines, the inter-annotator agreement (IAA) improved significantly, resulting in a higher IAA score of 86.05%. The purpose of constructing CS-A corpus is to increase the popularity of Cyber-Syndrome and draw attention to its subtle impact on people’s health. Meanwhile, annotated corpus promotes the development of natural language processing technology. Some model experiments can be implemented based on this corpus, such as optimizing and improving models for discontinuous entity recognition, nested entity recognition, etc. The CS-A corpus has been uploaded to figshare.

Abstract Meningeal lymphatic vessels (mLVs) play a pivotal role in regulating metabolic waste from cerebrospinal fluid (CSF). However, the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo. Here, we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system, including mLVs and glymphatic pathways. The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm, facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma. Subsequently, using this imaging technique, we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20–40 min after injection, along with determining the flow direction from CSF to lymph nodes. Inspiringly, in the Alzheimer’s disease (AD) mouse model, we observed that AD mice exhibit a ~ 70% reduction in drainage volume of mLVs compared to wild-type mice. With the development of AD, there is be continued decline in mLVs drainage volume. This finding clearly demonstrates that the AD mouse model has impaired CSF drainage. Our study opens up a horizon for understanding the brain’s drainage mechanism and dissecting mLVs-associated neurological disorders.

Abstract Introduction This systematic review and meta-analysis aimed to provide an updated evidence base for clinical decision-making by comparing the efficacy and safety of aflibercept 2 mg and ranibizumab in treating retinal vein occlusion (RVO). Methods A systematic search was conducted using eight databases up to December 2021. Randomized controlled trials (RCTs) and real-world studies (RWSs) comparing aflibercept and ranibizumab in patients with RVO were evaluated. The primary outcomes assessed were efficacy, number of injections administered, and adverse events. Results Three RCTs (424 patients) and 11 RWSs (1415 patients) were included. For central RVO (CRVO), RCTs demonstrated a comparable efficacy, whereas RWSs showed that mean changes from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were significantly greater with aflibercept compared to ranibizumab; the number of injections of aflibercept was fewer than that of ranibizumab in RCTs, but similar in RWSs. For branch RVO (BRVO), no statistically significant difference in efficacy between the two drugs in RCTs/RWSs was observed, with fewer injections of aflibercept at 12 months in RWSs. The safety profiles of both drugs were similar for both CRVO and BRVO. Conclusions For CRVO, aflibercept had similar efficacy and safety profile but with fewer injections versus ranibizumab in RCTs; RWSs showed greater BCVA improvement and CRT reduction with aflibercept than ranibizumab. For BRVO, RCTs showed similar in efficacy, safety, and injection numbers for both drugs, while RWSs demonstrated that aflibercept required fewer injections at 12 months of follow-up. Overall, this study provides updated evidence for clinical decision-making in the treatment of RVO.

Abstract Background Although abnormal accumulation of amyloid beta (Aβ) protein is thought to be the main cause of Alzheimer’s disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid β induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aβ deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. Methods Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aβ oligomer stereotactic injection model was established to explain the relationship between Aβ and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. Results Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aβ-injected model, suggesting a direct relationship between Aβ and vascular dysfunction. Pericytes showed impaired features including low PDGFRβ expression and increased pro-inflammatory chemokines secretion under the administration of Aβ in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. Conclusions Our results provide new insights into the pathogenic mechanism underlying Aβ-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.

BackgroundStroke is a devastating disease and ranks as the second leading cause of death and disability globally. Several studies have shown that preceding infection (PI) of upper respiratory tract are strongly associated with acute ischemic stroke (AIS). However, the clinical implications and underlying pathological mechanisms remain unclear.MethodsIn this study, 16S rRNA gene sequencing was employed to compare the structural characteristics of oropharyngeal and gut microbiota in AIS patients with or without PI and normal controls (NCs; 30 cases each), and systemic inflammatory markers were detected to explore the relationship between upper respiratory tract infections (URTIs) and subsequent stroke severity and functional outcome and the potential mechanism.ResultsWe found that patients with AIS-PI exhibited elevated serum WBC, NE, CRP, and Hcy levels, as well as a higher 90-day mRS score. Oropharyngeal and gut microbiota analysis showed that AIS and AIS-PI patients exhibited increased microbial richness in sequence. Principal coordinate analysis of the microbiota demonstrated significant differences in microbiota composition among the three groups. In AIS-PI patients, Megamonas, Megasphaera, Ruminococcaceae UCG 004, Rothia, and Streptococcus were significantly enriched in the gut. Opportunistic pathogens, including Thermus, uncultured Veillonella sp., and Oribacterium sinu, were found to be significantly enriched in the oropharynx. The dysregulated microbiota were positively correlated with systemic inflammatory markers, stroke severity, and poor prognosis. In contrast, short-chain fatty acid-producing bacteria Eisenbergiella, bacterium NLAE, Fusicatenibacter, Ruminococcaceae, and Faecalibacterium were enriched in NCs. Their abundances were negatively correlated with systemic inflammatory markers, stroke severity and poor prognosis.ConclusionOur findings suggest that PIs of the upper respiratory tract may contribute to poor short-term functional outcome in AIS patients by causing disturbance of the oropharyngeal and gut microbiota and promoting elevated systemic inflammation levels.

Objective: This study aimed to investigate the mechanism that Lactobacillus murinus (L. murinus) alleviated lung inflammation induced by polycyclic aromatic hydrocarbons (PAHs) exposure based on metabolomics. Methods: Female mice were administrated with PAHs mix, L. murinus and indoleacrylic acid (IA) or indolealdehyde (IAId). Microbial diversity in feces was detected by 16 S rRNA gene sequencing. Non-targeted metabolomics analysis in urine samples and targeted analysis of tryptophan metabolites in serum by UPLC-Orbitrap-MS and short-chain fatty acids (SCFA) in feces by GC-MS were performed, respectively. Flow cytometry was used to determine T helper immune cell differentiation in gut and lung tissues. The levels of IgE, IL-4 and IL-17A in the bronchoalveolar lavage fluid (BALF) or serum were detected by ELISA. The expressions of aryl hydrocarbon receptor (Ahr), cytochrome P450 1A1 (Cyp1a1) and forkheadbox protein 3 (Foxp3) genes and the histone deacetylation activity were detected by qPCR and by ELISA in lung tissues, respectively. Results: PAHs exposure induced lung inflammation and microbial composition shifts and tryptophan metabolism disturbance in mice. L. murinus alleviated PAHs-induced lung inflammation and inhibited T helper cell 17 (Th17) cell differentiation and promoted regulatory T cells (Treg) cell differentiation. L. murinus increased the levels of IA and IAId in the serum and regulated Th17/Treg imbalance by activating AhR. Additionally, L. murinus restored PAHs-induced decrease of butyric acid and valeric acid which can reduce the histone deacetylase (HDAC) level in the lung tissues, enhancing the expression of the Foxp3 gene and promoting Treg cell differentiation. Conclusion: our study illustrated that L. murinus alleviated PAHs-induced lung inflammation and regulated Th17/Treg cell differentiation by regulating host tryptophan metabolism and SCFA levels. The study provided new insights into the reciprocal influence between gut microbiota, host metabolism and the immune system, suggesting that L. murinus might have the potential as a novel therapeutic strategy for lung diseases caused by environmental pollution in the future.

We evaluated the HIV-1 DNA reservoir in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) in people with HIV (PWH) and associations to cognitive dysfunction. Using the intact proviral DNA assay (IPDA), an emerging technique to identify provirus that may be the source of viral rebound, we assessed HIV DNA in CSF and PBMC in PWH regardless of antiretroviral therapy (ART). CSF was used as a sampling surrogate for the central nervous system (CNS) as opposed to tissue. IDPA results (3′ defective, 5′ defective, and intact HIV DNA) were analyzed by compartment (Wilcoxon signed rank; matched and unmatched pairs). Cognitive performance, measured via a battery of nine neuropsychological (NP) tests, were analyzed for correlation to HIV DNA (Spearman's rho). 11 CSF and 8 PBMC samples from PWH were evaluated both unmatched and matched. Total CSF HIV DNA was detectable in all participants and was significantly higher than in matched PBMCs (p ​= ​0.0039). Intact CSF HIV DNA was detected in 7/11 participants and correlated closely with those in PBMCs but tended to be higher in CSF than in PBMC. CSF HIV DNA did not correlate with global NP performance, but higher values did correlate with worse executive function (p ​= ​0.0440). Intact HIV DNA is frequently present in the CSF of PWH regardless of ART. This further supports the presence of an HIV CNS reservoir and provides a method to study CNS reservoirs during HIV cure studies. Larger studies are needed to evaluate relationships with CNS clinical outcomes.

Objective: In order to solve the practical problem of uneven temperature distribution in the tunnel and easy adhesion of sandwich seaweed to the conveyor belt. Methods: The structure of tunnel baking equipment for sandwich seaweed and the software and hardware of fuzzy PID temperature control system were designed in this study, the baking device model was established based on the boundary conditions set in the actual production environment, after that, the CFD simulation optimization experiments was performed on the temperature field inside the tunnel. Results: The simulation experiment showed that the parameter combination of evenly arranged heating tubes, 30 heating tubes, 220 mm spacing, and 1 000 mm heating length was the most suitable for the baking of sandwich seaweed. It could be concluded from the prototype test that the optimized sandwich seaweed baking equipment had a uniform temperature distribution in the tunnel, a pasting frequency of ≤ 2 times/hour, a production efficiency of ≥ 1 000 pieces/hour, and a product quality consistency error of ≤ 2.1%, which met the actual production requirements of sandwich seaweed baking. Conclusion: The use of this device can effectively solve the problem of uneven temperature distribution inside the tunnel of traditional sandwich seaweed tunnel baking equipment, and meet the actual production requirements of sandwich seaweed baking.

The first operational version of the coupled Hurricane Analysis and Forecast System (HAFSv1) launched in 2023 consists of the HYbrid Coordinate Ocean Model (HYCOM) and finite-volume cubed-sphere (FV3) dynamic atmosphere model. This system is a product of efforts involving improvements and updates over a 4-year period (2019–2022) through extensive collaborations between the Environmental Modeling Center at the US National Centers for Environmental Prediction (NCEP) and NOAA Atlantic Oceanography and Meteorology Laboratory. To provide two sets of numerical guidance, the initial operational capability of HAFSv1 was configured to two systems—HFSA and HFSB. In this study, we present in-depth analysis of the forecast skills of the upper ocean that was co-evolved by the HFSA and HFSB. We chose hurricane Laura (2020) as an example to demonstrate the interactions between the storm and oceanic mesoscale features. Comparisons performed with the available in situ observations from gliders as well as Argos and National Data Buoy Center moorings show that the HYCOM simulations have better agreement for weak winds than high winds (greater than Category 2). The skill metrics indicate that the model sea-surface temperature (SST) and mixed layer depth (MLD) have a relatively low correlation. The SST, MLD, mixed layer temperature (MLT), and ocean heat content (OHC) are negatively biased. For high winds, SST and MLT are more negative, while MLD is closer to the observations with improvements of about 8%–19%. The OHC discrepancy is proportional to predicted wind intensity. Contrarily, the mixed layer salinity (MLS) uncertainties are smaller and positive for higher winds, probably owing to the higher MLD. The less-negative bias of MLD for high winds implies that the wind-force mixing is less effective owing to the higher MLD and high buoyancy stability (approx. 1.5–1.7 times) than the observations. The heat budget analysis suggests that the maximum heat loss by hurricane Laura was O(< 3°C per day). The main contributor here is advection, followed by entrainment, which act against or with each other depending on the storm quadrant. We also found relatively large unaccountable heat residuals for the in-storm period, and the residuals notably led the heat tendency, meaning that further improvements of the subscale simulations are warranted. In summary, HYCOM simulations showed no systematic differences forced by either HFSA or HFSB.

BackgroundCoinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5–67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus.Case presentationA 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography.ConclusionWe first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.

BackgroundEmergency departments (EDs) are complex and fast-paced clinical settings where a diagnosis is made in a time-, information-, and resource-constrained context. Thus, it is predisposed to suboptimal diagnostic outcomes, leading to errors and subsequent patient harm. Arriving at a timely and accurate diagnosis is an activity that occurs after an effective collaboration between the patient or caregiver and the clinical team within the ED. Interventions such as novel sociotechnical solutions are needed to mitigate errors and risks. ObjectiveThis study aims to identify challenges that frontline ED health care providers and patients face in the ED diagnostic process and involve them in co-designing technological interventions to enhance diagnostic excellence. MethodsWe will conduct separate sessions with ED health care providers and patients, respectively, to assess various design ideas and use a participatory design (PD) approach for technological interventions to improve ED diagnostic safety. In the sessions, various intervention ideas will be presented to participants through storyboards. Based on a preliminary interview study with ED patients and health care providers, we created intervention storyboards that illustrate different care contexts in which ED health care providers or patients experience challenges and show how each intervention would address the specific challenge. By facilitating participant group discussion, we will reveal the overlap between the needs of the design research team observed during fieldwork and the needs perceived by target users (ie, participants) in their own experience to gain their perspectives and assessment on each idea. After the group discussions, participants will rank the ideas and co-design to improve our interventions. Data sources will include audio and video recordings, design sketches, and ratings of intervention design ideas from PD sessions. The University of Michigan Institutional Review Board approved this study. This foundational work will help identify the needs and challenges of key stakeholders in the ED diagnostic process and develop initial design ideas, specifically focusing on sociotechnological ideas for patient-, health care provider–, and system-level interventions for improving patient safety in EDs. ResultsThe recruitment of participants for ED health care providers and patients is complete. We are currently preparing for PD sessions. The first results from design sessions with health care providers will be reported in fall 2024. ConclusionsThe study findings will provide unique insights for designing sociotechnological interventions to support ED diagnostic processes. By inviting frontline health care providers and patients into the design process, we anticipate obtaining unique insights into the ED diagnostic process and designing novel sociotechnical interventions to enhance patient safety. Based on this study’s collected data and intervention ideas, we will develop prototypes of multilevel interventions that can be tested and subsequently implemented for patients, health care providers, or hospitals as a system. International Registered Report Identifier (IRRID)DERR1-10.2196/55357

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%–13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts.

Lightweight Al-based entropy alloys are newly emerged materials with promising potential for structural applications; however, their modeling and strengthening prediction require further exploration. In this study, the spatial distributions of various phases in three Al-based entropy alloys were investigated. A closely interconnected intermetallic compound (IC) network comprising Al2Cu and Al45Cr7 phases was identified. Finite element (FE) modeling was conducted based on the reconstructed three-dimensional microstructure to simulate compressive deformation behavior. The IC network served as the main stress bearer during deformation. Thin sections in the Al2Cu network were the weak sites where stress concentration and damage first occurred. However, the breakage of this limited region contributes to relatively coordinated deformation and extended plasticity. The breakage of large particles accounts for the final alloy failure. The results of the FE model were compared with the experimentally measured stress–strain behavior and mechanical properties, showing very good agreement. Given the non-uniform distribution of strain and stress during deformation, a strengthening model, merging the Voigt and Reuss models, was also developed to predict the mechanical properties of Al-based entropy alloys with the aim of facilitating Al-based entropy alloy development.

Sudden infant death syndrome is one of the leading causes of post-neonatal mortality. The thymic-lymphatic condition in children is a clinically rare manifestation and difficult to diagnose condition, assessed as a background, realized in a number of cases of sudden death syndrome. However, the clinical and histopathological manifestations of thymic-lymphatic status may not be clearly expressed. We present an unusual case of sudden infant death syndrome as a result of thymic-lymphatic dysgenesis complicated by acute adrenal insufficiency.

Abstract Background Alzheimer's disease (AD) is a neurodegenerative disorder and the predominant type of dementia worldwide. It is characterized by the progressive and irreversible decline of cognitive functions. In addition to the pathological beta-amyloid (Aβ) deposition, glial activation, and neuronal injury in the postmortem brains of AD patients, increasing evidence suggests that the often overlooked vascular dysfunction is an important early event in AD pathophysiology. Vascular endothelial growth factor (VEGF) plays a critical role in regulating physiological functions and pathological changes in blood vessels, but whether VEGF is involved in the early stage of vascular pathology in AD remains unclear. Methods We used an antiangiogenic agent for clinical cancer treatment, the humanized monoclonal anti-VEGF antibody bevacizumab, to block VEGF binding to its receptors in the 5×FAD mouse model at an early age. After treatment, memory performance was evaluated by a novel object recognition test, and cerebral vascular permeability and perfusion were examined by an Evans blue assay and blood flow scanning imaging analysis. Immunofluorescence staining was used to measure glial activation and Aβ deposits. VEGF and its receptors were analyzed by enzyme-linked immunosorbent assay and immunoblotting. RNA sequencing was performed to elucidate bevacizumab-associated transcriptional signatures in the hippocampus of 5×FAD mice. Results Bevacizumab treatment administered from 4 months of age dramatically improved cerebrovascular functions, reduced glial activation, and restored long-term memory in both sexes of 5×FAD mice. Notably, a sex-specific change in different VEGF receptors was identified in the cortex and hippocampus of 5×FAD mice. Soluble VEGFR1 was decreased in female mice, while full-length VEGFR2 was increased in male mice. Bevacizumab treatment reversed the altered expression of receptors to be comparable to the level in the wild-type mice. Gene Set Enrichment Analysis of transcriptomic changes revealed that bevacizumab effectively reversed the changes in the gene sets associated with blood–brain barrier integrity and vascular smooth muscle contraction in 5×FAD mice. Conclusions Our study demonstrated the mechanistic roles of VEGF at the early stage of amyloidopathy and the protective effects of bevacizumab on cerebrovascular function and memory performance in 5×FAD mice. These findings also suggest the therapeutic potential of bevacizumab for the early intervention of AD.

Abstract Background Cancer-related psychological and physical disorders can mean stressful and painful experiences for patients. Art therapy, a form of complementary and alternative medicine, is an increasingly popular way to decrease emotional stress, alleviate somatic symptoms, and improve quality of life in patients with cancer. However, current systematic reviews have not explored the beneficial effects of art therapy. Moreover, there have been inconsistent findings on the effect of this therapy, and there is insufficient evidence to confirm the effects in adults with cancer. The objective of this study was to determine the efficacy of art therapy in improving quality of life and psychosomatic symptoms in adults with cancer. Methods This systematic review and meta-analysis included adults with all kinds of cancer. Six English-language and three large Chinese-language databases were comprehensively searched for relevant studies. Gray literature and references were also checked. The quality of the included studies was evaluated using the Cochrane risk-of-bias assessment tool. Results Eight eligible randomized controlled trials conducted in four countries were included. Art therapy improved overall quality of life, but had no significant effect on psychological health or physical health sub-dimensions in women with cancer. Moreover, art therapy alleviated anxiety and depression, but had only a tendency toward an effect on somatic symptoms. Conclusions Moderate-quality evidence shows that art therapy is beneficial for women with cancer in terms of improving the overall quality of life and alleviating emotional symptoms (anxiety and depression). However, more high-quality randomized controlled trials are needed to determine the efficacy of this therapy on somatic symptoms.

Abstract Background Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in different types of solid tumors. This study aimed to evaluate the prognostic importance of LAG3 and its role in the immune system within solid tumors. Methods Extensive literature searches were conducted using the Pubmed, EMBASE, and Cochrane Library databases to identify relevant studies exploring the effect of LAG3 on survival outcomes. Pooled hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to evaluate the prognostic values of LAG3. Afterwards, subgroup analysis and sensitivity analysis were conducted. Pan-cancer analysis investigated the possible relationships between LAG3 expression and genetic alterations, RNA methylation modification-related genes, genomic instability, immune checkpoint genes, and infiltration of immune cells. Results A total of 43 studies with 7,118 patients were included in this analysis. Higher expression of LAG3 was associated with worse overall survival (HR = 1.10, 95% CI 1.01–1.19, P = 0.023), but not disease-free survival (HR = 1.41, 95% CI 0.96–2.07, P = 0.078), progression-free survival (HR = 1.12, 95% CI 0.90–1.39, P = 0.317) or recurrence-free survival (HR = 0.98, 95% CI 0.81–1.19, P = 0.871). Subgroup analysis showed that LAG3 might play different prognostic roles in different solid tumors. LAG3 expression was positively associated with immune cell infiltration and immune checkpoint genes in all of the cancers included. LAG3 expression was also found to be associated with microsatellite instability (MSI), copy number variation (CNV), simple nucleoside variation (SNV), tumor mutation burden (TMB), and neoantigen in various types of cancers. Conclusions Elevated expression of LAG3 is linked to poorer prognosis among patients diagnosed with solid cancers. LAG3 might play varying prognostic roles in different types of solid tumors. Given its substantial involvement in cancer immunity and tumorigenesis, LAG3 has garnered attention as a promising prognostic biomarker and a potential target for immunotherapy.

Check dams play a pivotal role in debris flow prevention and control engineering. However, their disaster prevention and mitigation capacity gradually decrease over service time due to repeated debris flow impacts. The study was carried out in 15 ditches and 55 check dams within Wudu District, Longnan City, Gansu Province. Seven key evaluation factors were selected for effectiveness and safety: reservoir siltation ratio, slope stability, drainage hole blockage, dam body damage, dam foundation damage, dam shoulder damage, and safety. The evaluation model of the serviceability of the indivusual dam and the comprehensive serviceability of the single trench of the barrage was established by using hierarchical analysis and fuzzy comprehensive evaluation method, and the serviceability was divided into four grades: excellent, good, medium and poor. The evaluation results show that the serviceability rating of individual dams is predominately "poor", accounting for 34.5%. Similarly, the collective serviceability rating of single trench dams for debris flow is predominately "poor", at 33.3%. The results of the evaluation are consistent with the fieldwork observations, providing a valuable reference for predicting the service performance and service life of barrage dams.

Inflammatory bowel disease (IBD) is a systemic disorder affecting intestinal tract and other organs outside the gut, known as extraintestinal manifestations (EIMs). These EIMs are complex and diverse, and early treatment may reduce teratogenic rates and improve quality of life. However, our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight. Fortunately, advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs. The gut microbiota can drive aberrant immune activation and intestinal inflammation. Intriguingly, chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis. Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function. Furthermore, gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites, leading to systemic inflammatory responses. The microbiome is showing its potential in treating IBD and EIMs, and microbial engineering approaches, such as probiotic engineering and engineered fecal microbiota transplantation, are exhibiting great promise for IBD therapeutics.

This paper presents a rapidly exploring random tree (RRT) algorithm with an effective post waypoint shift, which is suitable for the path planning of a wheeled mobile robot under kinematic constraints. In the growth of the exploring tree, the nearest node that satisfies the kinematic constraints is selected as the parent node. Once the distance between the new node and the target is within a certain threshold, the tree growth stops and a target connection based on minimum turning radius arc is proposed to generate an initial complete random path. The most significant difference from traditional RRT-based methods is that the proposed method optimizes the path based on Dubins curves through a post waypoint shift after a random path is generated, rather than through parent node selection and rewiring during the exploring tree growth. Then, it is proved that the method can obtain an optimal path in terms of the shortest length. The optimized path has good convergence and almost does not depend on the state of the initial random path. The comparative test results show that the proposed method has significant advantages over traditional RRT-based methods in terms of the sampling point number, the tree node number, and the path node number. Subsequently, an efficient method is further proposed to avoid unknown obstacles, which utilizes the original path information and thus effectively improves the new path planning efficiency. Simulations and real-world tests are carried out to demonstrate the effectiveness of this method.

This study was conducted to investigate the impact of EGCG on antioxidant stress, immune response, and intestinal microbiota flora in post-weaning rabbits. A total of 144 40 d Ira rabbits (equally divided by sex), were randomly allocated to six treatments. with five groups receiving doses of 200, 400, 600, 800, and 1000 mg/kg of EGCG, while one group served as a control without EGCG. Over 48 days, this study the assessed growth performance, antioxidant capacity, immune system, intestinal morphology, and cecal microbiota in the rabbits. The results showed that EGCG did not affect growth performance; however, significant linear and quadratic correlations were observed between the MDA, T-AOC, and GSH-Px activities in the liver and jejunum (p < 0.05). Quadratic effects were observed for the spleen and thymus indexes and serum IgG levels with increasing EGCG dosages (p < 0.05). Additionally, positive linear and quadratic effects were found on the ileal villus height and the villus height/crypt depth ratio. The relative abundances of Euryarchaeota, Patescibacteria, and Synergistota were significantly enriched in rabbits fed with high dosages (600–1000 mg/kg) of EGCG. Conclusively, the addition of large doses of EGCG (400–800 mg/kg) can effectively suppress oxidative stress and alleviate weaning stress, thereby contributing to the protection of post-weaning rabbits.

The Model for Prediction Across Scales-Atmosphere (MPAS) was used to simulate meteorological conditions for a two-week winter episode during 10–23 January 2013, and a two-week summer episode during 18–31 July 2016, using both as a global model and a regional model with a focus on California. The results of both global and regional applications of MPAS were compared against the surface and upper air rawinsonde observations while the variations of characteristic meteorological variables and modeling errors were evaluated in space, time, and statistical sense. The results of the Advanced Weather Research and Forecast (WRF-ARW, hereafter WRF) model simulations for the same episodes were also used to evaluate the results of both applications of MPAS. The temporal analyses performed at surface stations indicate that both global and regional applications of MPAS and WRF model predict the diurnal evolution of characteristic meteorological parameters reasonably well in both winter and summer episodes studied here. The average diurnal bias in predicting 2 m temperature by MPAS and WRF are about the same with a maximum of 2 °C in winter and 1 °C in summer while that of 2 m mixing ratio is within 1 g/kg for all three modeling applications. The rawinsonde profiles of temperature, dew point temperature, and wind direction agree reasonably well with observations while wind speed is underestimated by all three applications. The comparisons of the spatial distribution of anomaly correlation and mean bias errors calculated from each model results for 2 m temperature, 2 m water vapor mixing ratio, 10 m wind speed and wind direction indicate that all three models have similar magnitudes of agreement with observations as well as errors away from observations throughout California.

An investigation is undertaken to explore a sudden quasi-linear precipitation and gale event that transpired in the afternoon of 30 May 2024 over Beijing. It was situated at the southwestern periphery of a double-center low-vortex system, where a moisture-rich belt efficiently channeled abundant warm, humid air northward from the south. The interplay between dynamical lifting, convergent airflow-induced uplift, and the amplifying effects of the northern mountainous terrain’s topography creates favorable conditions that support the development and persistence of quasi-linear convective precipitation, accompanied by gale-force winds at the surface. The study also analyzes the impacts of five microphysics schemes (Lin, WSM6, Goddard, Morrison, and WDM6) employed in a weather research and forecasting (WRF) numerical model, with which the simulated rainfall and radar reflectivity are compared against ground-based rain gauge network and weather radar observations, respectively. Simulations with the five microphysics schemes demonstrate commendable skills in replicating the macroscopic quasi-linear pattern of the event. Among the schemes assessed, the WSM6 scheme exhibits its superior agreement with radar observations. The Morrison scheme demonstrates superior performance in predicting cumulative rainfall. Nevertheless, five microphysics schemes exhibit limitations in predicting the rainfall amount, the rainfall duration, and the rainfall area, with a discernible lag of approximately 30 min in predicting precipitation onset, indicating a tendency to forecast peak rainfall events slightly posterior to their true occurrence. Furthermore, substantial disparities emerge in the simulation of the vertical distribution of hydrometeors, underscoring the intricacies of microphysical processes.

Background and objectivesThe oral and gut microbiota play significant roles in childhood asthma pathogenesis. However, the communication dynamics and pathogenic mechanisms by which oral microbiota influence gut microbiota and disease development remain incompletely understood. This study investigated potential mechanisms by which oral-originated gut microbiota, specifically Prevotella genus, may contribute to childhood asthma etiology.MethodsOral swab and fecal samples from 30 asthmatic children and 30 healthy controls were collected. Microbiome composition was characterized using 16S rRNA gene sequencing and metagenomics. Genetic distances identified potential oral-originated bacteria in asthmatic children. Functional validation assessed pro-inflammatory properties of in silico predicted microbial mimicry peptides from enriched asthma-associated species. Fecal metabolome profiling combined with metagenomic correlations explored links between gut microbiota and metabolism. HBE cells treated with Prevotella bivia culture supernatant were analyzed for lipid pathway impacts using UPLC-MS/MS.ResultsChildren with asthma exhibited distinct oral and gut microbiota structures. Prevotella bivia, P. disiens, P. oris and Bacteroides fragilis were enriched orally and intestinally in asthmatics, while Streptococcus thermophilus decreased. P. bivia, P. disiens and P. oris in asthmatic gut likely originated orally. Microbial peptides induced inflammatory cytokines from immune cells. Aberrant lipid pathways characterized asthmatic children. P. bivia increased pro-inflammatory and decreased anti-inflammatory lipid metabolites in HBE cells.ConclusionThis study provides evidence of Prevotella transfer from oral to gut microbiota in childhood asthma. Prevotella’s microbial mimicry peptides and effects on lipid metabolism contribute to disease pathogenesis by eliciting immune responses. Findings offer mechanistic insights into oral-gut connections in childhood asthma etiology.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using ''Immunedeconv'' package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.