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Abstract Electrocatalytic semihydrogenation of acetylene (C2H2) provides a facile and petroleum-independent strategy for ethylene (C2H4) production. However, the reliance on the preseparation and concentration of raw coal-derived C2H2 hinders its economic potential. Here, a concave surface is predicted to be beneficial for enriching C2H2 and optimizing its mass transfer kinetics, thus leading to a high partial pressure of C2H2 around active sites for the direct conversion of raw coal-derived C2H2. Then, a porous concave carbon-supported Cu nanoparticle (Cu-PCC) electrode is designed to enrich the C2H2 gas around the Cu sites. As a result, the as-prepared electrode enables a 91.7% C2H4 Faradaic efficiency and a 56.31% C2H2 single-pass conversion under a simulated raw coal-derived C2H2 atmosphere (~15%) at a partial current density of 0.42 A cm−2, greatly outperforming its counterpart without concave surface supports. The strengthened intermolecular π conjugation caused by the increased C2H2 coverage is revealed to result in the delocalization of π electrons in C2H2, consequently promoting C2H2 activation, suppressing hydrogen evolution competition and enhancing C2H4 selectivity.

Abstract Background The monocot chimeric jacalins (MCJ) proteins, which contain a jacalin-related lectin (JRL) domain and a dirigent domain (DIR), are specific to Poaceae. MCJ gene family is reported to play an important role in growth, development and stress response. However, their roles in maize have not been thoroughly investigated. Results In this study, eight MCJ genes in the maize genome (designated as ZmMCJs) were identified, which displayed unequal distribution across four chromosomes. Phylogenetic relationships between the ZmMCJs were evident through the identification of highly conserved motifs and gene structures. Analysis of transcriptome data revealed distinct expression patterns among the ZmMCJ genes, leading to their classification into four different modules, which were subsequently validated using RT-qPCR. Protein structures of the same module are found to be relatively similar. Subcellular localization experiments indicated that the ZmMCJs are mainly located on the cell membrane. Additionally, hemagglutination and inhibition experiments show that only part of the ZmMCJs protein has lectin activity, which is mediated by the JRL structure, and belongs to the mannose-binding type. The cis-acting elements in the promoter region of ZmMCJ genes predicted their involvement response to phytohormones, such as abscisic acid and jasmonic acid. This suggests that ZmMCJ genes may play a significant role in both biotic and abiotic stress responses. Conclusions Overall, this study adds new insights into our understanding of the gene-protein architecture, evolutionary characteristics, expression profiles, and potential functions of MCJ genes in maize.

Abstract The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p

Abstract Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Abstract Large language models (LLMs) are seen to have tremendous potential in advancing medical diagnosis recently, particularly in dermatological diagnosis, which is a very important task as skin and subcutaneous diseases rank high among the leading contributors to the global burden of nonfatal diseases. Here we present SkinGPT-4, which is an interactive dermatology diagnostic system based on multimodal large language models. We have aligned a pre-trained vision transformer with an LLM named Llama-2-13b-chat by collecting an extensive collection of skin disease images (comprising 52,929 publicly available and proprietary images) along with clinical concepts and doctors’ notes, and designing a two-step training strategy. We have quantitatively evaluated SkinGPT-4 on 150 real-life cases with board-certified dermatologists. With SkinGPT-4, users could upload their own skin photos for diagnosis, and the system could autonomously evaluate the images, identify the characteristics and categories of the skin conditions, perform in-depth analysis, and provide interactive treatment recommendations.

Abstract Background β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin. Results This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium. Conclusions This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.

Abstract Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.

Abstract Objective This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk. Methods Clinical, pathological, and imaging data of 102 patients with surgically and pathologically confirmed meningiomas were retrospectively analyzed. Patients were divided into recurrence and non-recurrence groups based on follow-up. Tumor-infiltrating CD8 + T cells in tissue samples were quantitatively assessed with immunohistochemical staining. Apparent diffusion coefficient (ADC) histogram parameters from preoperative MRI were quantified in MaZda. Considering the high correlation between ADC histogram parameters, we only chose ADC histogram parameter that had the best predictive efficacy for COX regression analysis further. A visual nomogram was then constructed and the recurrence probability at 1- and 2-years was determined. Finally, subgroup analysis was performed with the nomogram. Results The risk factors for meningioma recurrence were ADCp1 (hazard ratio [HR] = 0.961, 95% confidence interval [95% CI]: 0.937 ~ 0.986, p = 0.002) and CD8 + T cells (HR = 0.026, 95%CI: 0.001 ~ 0.609, p = 0.023). The resultant nomogram had AUC values of 0.779 and 0.784 for 1- and 2-years predicted recurrence rates, respectively. The survival analysis revealed that patients with low CD8 + T cells counts or ADCp1 had higher recurrence rates than those with high CD8 + T cells counts or ADCp1. Subgroup analysis revealed that the AUC of nomogram for predicting 1-year and 2-year recurrence of WHO grade 1 and WHO grade 2 meningiomas was 0.872 (0.652) and 0.828 (0.751), respectively. Conclusions Preoperative ADC histogram parameters and tumor-infiltrating CD8 + T cells may be potential biomarkers in predicting meningioma recurrence risk. Clinical relevance statement The findings will improve prognostic accuracy for patients with meningioma and potentially allow for targeted treatment of individuals who have the recurrent form.

ABSTRACT Importance Postzygotic mutations in the GNAQ/GNA11 genes, which encode the G‐protein nucleotide binding protein alpha subunits, have been identified in patients with phakomatosis pigmentovascularis (PPV). However, little is known about the Chinese population. Objective To identify pathogenic mutations in pediatric patients with PPV within the Chinese population. Methods We performed whole‐exome sequencing (WES) using skin lesion tissues from pediatric patients diagnosed with PPV. Additionally, ultradeep‐targeted sequencing was conducted to validate the somatic mutations. A genotype‐phenotype correlation was analyzed by integrating data from previous reports with the findings of the present study. Results Thirteen patients were enrolled, all diagnosed with the cesioflammea type of PPV, except for one patient with an unclassifiable type. We identified somatic GNA11 c.547C>T (p.R183C) variant in seven patients and GNAQ c.548G>A (p.R183Q) in four patients, with low allelic fractions ranging from 2.1% to 8.6% through ultradeep sequencing. Besides, a GNAQ c.548G>A (p.R183Q) variant was detected through targeted sequencing in one of two patients who did not exhibit detectable variants via WES. The genotype‐phenotype correlation analysis, involving 15 patients with a GNA11 variant and 10 with a GNAQ variant, revealed that facial capillary malformation (87% vs. 50%, P = 0.075) and ocular melanocytosis (80% vs. 40%, P = 0.087) appeared to be more frequent in patients with GNA11 mutation compared to those with GNAQ mutations. All four patients diagnosed with cesiomarmorata type or overlapping cesioflammea and cesiomarmorata type PPV carried the GNA11 variant. Interpretation Our study demonstrated that the majority of PPV patients in the Chinese population carried a postzygotic variant of GNAQ/GNA11, thus further confirming the pathogenic role of GNAQ/GNA11 mosaicism in the development of PPV cesioflammea type.

Abstract High-quality ocean in situ profile observations are fundamental for ocean and climate research and operational oceanographic applications. Here we describe a new global ocean subsurface temperature profile database named the Chinese Academy of Science (CAS) Oceanography Data Center version 1 (CODC-v1). This database contains over 17 million temperature profiles between 1940–2023 from all available instruments. The major data source is the World Ocean Database (WOD), but CODC-v1 also includes some data from some Chinese institutes which are not available in WOD. The data are quality-controlled (QC-ed) by a new QC system that considers the skewness of local temperature distributions, topographic barriers, and the shift of temperature distributions due to climate change. Biases in Mechanical Bathythermographs (MBTs), eXpendable Bathythermographs (XBTs), and Bottle data (OSD) are all corrected using recently proposed correction schemes, which makes CODC-v1 a bias-corrected dataset. These aspects ensure the data quality of the CODC-v1 database, making it suitable for a wide spectrum of ocean and climate research and applications.

Abstract The high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D2O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D2O with an 80% FE at −100 mA cm−2. The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at −100 mA cm−2 rationalizes the design concept.

Abstract Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.

Abstract Proteins and nucleic-acids are essential components of living organisms that interact in critical cellular processes. Accurate prediction of nucleic acid-binding residues in proteins can contribute to a better understanding of protein function. However, the discrepancy between protein sequence information and obtained structural and functional data renders most current computational models ineffective. Therefore, it is vital to design computational models based on protein sequence information to identify nucleic acid binding sites in proteins. Here, we implement an ensemble deep learning model-based nucleic-acid-binding residues on proteins identification method, called SOFB, which characterizes protein sequences by learning the semantics of biological dynamics contexts, and then develop an ensemble deep learning-based sequence network to learn feature representation and classification by explicitly modeling dynamic semantic information. Among them, the language learning model, which is constructed from natural language to biological language, captures the underlying relationships of protein sequences, and the ensemble deep learning-based sequence network consisting of different convolutional layers together with Bi-LSTM refines various features for optimal performance. Meanwhile, to address the imbalanced issue, we adopt ensemble learning to train multiple models and then incorporate them. Our experimental results on several DNA/RNA nucleic-acid-binding residue datasets demonstrate that our proposed model outperforms other state-of-the-art methods. In addition, we conduct an interpretability analysis of the identified nucleic acid binding residue sequences based on the attention weights of the language learning model, revealing novel insights into the dynamic semantic information that supports the identified nucleic acid binding residues. SOFB is available at https://github.com/Encryptional/SOFB and https://figshare.com/articles/online_resource/SOFB_figshare_rar/25499452 .

Abstract Purpose To evaluate the intracavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). Methods Thirty AMI patients and twenty controls were examined via CMR, which included cine imaging, late gadolinium enhancement (LGE) and global heart 4D flow imaging. The KE parameters were indexed to LV end-diastolic volume (EDV) to obtain average, systolic and diastolic KE as well as the proportion of LV in-plane KE (%). These parameters were compared between the AMI patients and controls and between the two subgroups. Results Analysis of the LV blood flow KE parameters at different levels of the LV cavity and in different segments of the same level showed that the basal level had the highest blood flow KE while the apical level had the lowest in the control group. There were no significant differences in diastolic KE, systolic in-plane KE and diastolic in-plane KE between the anterior wall and posterior wall (p > 0.05), only the systolic KE had a significant difference between them (p

For the pressurized water reactor two-step calculation, the traditional assembly homogenization and two-group neutron diffusion calculation have been widely used. When it comes to the core pin-by-pin simulation, many models and techniques are different and unsettled. In this paper, the homogenization methods based on the pin discontinuity factors and super homogenization factors are used to get the pin-cell homogenized parameters. The heterogeneous leakage model is applied to modify the infinite flux spectrum of the single assembly with reflective boundary condition and to determine the diffusion coefficients for the SP3 solver which is used in the core simulation. To reduce the environment effect of the single-assembly reflective boundary condition, the on-line method for the SPH factors updating is applied in this paper, and the functionalization of SPH factors based on the least-squares method will be pre-made alone with the table of the group constants. The fitting function will be used to update the thermal-group SPH factors with a whole-core pin-by-pin homogeneous solution on-line. The three-dimensional Watts Bar Nuclear Unit 1 (WBN1) problem was utilized to test the performance of pin-by-pin calculation. And numerical results have demonstrated that PWR pin-by-pin core calculation has more accurate results compared with the traditional assembly-homogenization scheme.

Acinetobacter baumannii is a pathogenic bacterium widespread in human environments, especially in intensive care units, and is associated with high morbidity and infection rates. Multiple drug resistance in A. baumannii frequently leads to the death of patients, making the development of multi-effect antibacterial agents against this bacterium a research hotspot. We have previously found that the X33 antimicrobial oligopeptide can effectively inhibit the growth of Penicillium digitatum and Candida albicans. Herein, we evaluated the antibacterial activity of X33 antimicrobial oligopeptide against A. baumannii by determining the minimum inhibitory concentration, inhibition zone, and growth curve. The increase in extracellular alkaline phosphatase and the leakage of intracellular compounds confirmed the effect of X33 antimicrobial oligopeptide on the cell wall and membrane. Changes in reactive oxygen species, malondialdehyde, ATP, reducing sugar, soluble protein, and pyruvate content demonstrated that the incubation with X33 antimicrobial oligopeptide affected energy metabolism and oxidative stress. Consistent with the physiological characteristics, transcriptomics analysis indicated that incubation with X33 antimicrobial oligopeptide significantly induced changes in the expression of 2339 genes, including 1262 upregulated and 1077 downregulated genes, which participate in oxidative phosphorylation, ribosome, quorum sensing, fatty acid degradation, glycolysis/gluconeogenesis, and citrate cycle pathways. These results provide a fundamental basis for investigating the mechanism of X33 antimicrobial oligopeptide as a potential drug against A. baumannii.

Abstract Inhibitors of α‐amylase have been developed to regulate postprandial blood glucose fluctuation. The enzyme inhibition arises from direct or indirect inhibitor‐enzyme interactions, depending on inhibitor structures. However, an ignored factor, substrate, may also influence or even decide the enzyme inhibition. In this work, it is innovatively found that the difference in substrate enzymolysis modes, i.e., structural composition and concentration of α‐1,4‐glucosidic bonds, triggers the diversity in inhibitor‐enzyme aggregating behaviors and α‐amylase inhibition. For competitive inhibition, there exists an equilibrium between α‐amylase‐substrate catalytic affinity and inhibitor‐α‐amylase binding affinity; therefore, a higher enzymolysis affinity and concentration of α‐1,4‐glucosidic structures interferes the balance, unfavoring inhibitor‐enzyme aggregate formation and thus weakening α‐amylase inhibition. For uncompetitive inhibition, the presence of macromolecular starch is necessary instead of micromolecular GalG2CNP, which not only binds with active site but with an assistant flexible loop (involving Gly304‐Gly309) near the site. Hence, the refined enzyme structure due to the molecular flexibility more likely favors the inhibitor binding with the non‐active loop, forming an inhibitor‐enzyme‐starch ternary aggregate. Conclusively, this study provides a novel insight into the evaluation of α‐amylase inhibition regarding the participating role of substrate in inhibitor‐enzyme aggregating interactions, emphasizing the selection of appropriate substrates in the development and screening of α‐amylase inhibitors.

Abstract The effectiveness of Toll‐like 9 agonists (CpG) as an adjuvant for tumor immunotherapy is restricted due to their insufficient ability to activate anti‐tumor immunity. To address that, the common nutrient metal ions are explored (Mn2+, Cu2+, Ca2+, Mg2+, Zn2+, Fe3+, and Al3+), identifying Mn2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING‐NF‐κB pathway. Mn2+ and CpG are then self‐assembled with epigallocatechin gallate (EGCG) into a nanoadjuvant MPN/CpG. Local delivery of MPN/CpG effectively inhibits tumor growth in a B16 melanoma‐bearing mouse model, reshaping the tumor microenvironment (TME) by repolarizing M2‐type tumor‐associated macrophages (TAMs) to an M1‐type and boosting intra‐tumoral infiltration of CD8+/CD4+ T lymphocytes and DCs. Furthermore, compared to free CpG, MPN/CpG exhibits heightened accumulation in lymph nodes, enhancing CpG uptake and DC activation, consequently inducing significant antigen‐specific cytotoxic CD8+ T cell immune response and humoral immunity. In a prophylactic tumor‐bearing mouse model, MPN/CpG vaccination with OVA antigen significantly delays B16‐OVA melanoma growth and extends mouse survival. These findings underscore the potential of MPN/CpG as a multifunctional adjuvant platform to drive powerful innate and adaptive immunity and regulate TME against tumors.

Strongly scattering media disrupt both the wavefront distribution and the polarization state of the incident light field. Controlling and effectively utilizing depolarization effects are crucial for optical applications in highly scattering environments, such as imaging through dense fog. However, current simulation models have difficulty simulating the evolution of vector light fields within scattering media, posing challenges for studying vector light fields in strongly scattering environments. Here, we propose the Vector Angular Spectrum (VAS) model for simulating the propagation of vector light fields within scattering media. By introducing the angular spectrum distribution of vector light scattering and polarization conversion mechanisms, this model can simulate the depolarization effects of vector light propagating through strongly scattering media. The VAS model has also been used to investigate the focusing of vector scattered light through scattering media. Furthermore, the simulation results of the model have been validated through experiments. The proposed VAS model is expected to play a role in the theoretical research of vector scattered light and optical applications in strongly scattering environments.

Abstract The north‐south seismic belt of China poses a high risk of earthquakes, necessitating the need for accurate and rapid prediction of intensity measures (IMs) to prevent and mitigate potential damage. We have developed a new multi‐task model, CRAQuake, to predict IMs for the north‐south seismic belt of China. Using initial arrival seismic waves recorded at a single station as input, CRAQuake simultaneously predicts six IMs without relying on pre‐configured parameters such as earthquake source, path, and location. The model was trained on 4,281 sets of strong motion records data sets at 822 stations and tested to show highly correlated results with the target IMs. The prediction performance continues to improve as the input initial arrival seismic wave time window increases. CRAQuake promises to enhance the accuracy and timeliness of IMs prediction in the north‐south seismic belt of China.

ObjectiveThis study aims to examine the mental health of patients with lumbar disc herniation with radiculopathy (LDHR) and to evaluate the effects of percutaneous transforaminal endoscopic discectomy (PTED) on their mental well-being.MethodThis study included 114 LDHR patients who received PTED in the Spinal Orthopedics Department of Zhongshan Hospital of Traditional Chinese Medicine between May 2022 and May 2023. The study population was stratified into two groups according to the presence of preoperative anxiety and depression: Group A comprised patients with such symptoms, and Group B included the remainder. Patients were assessed using the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale for Pain (VAS), and the Oswestry Disability Index (ODI) at preoperative and final follow-up visits. Evaluations were performed using the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale, and the Oswestry Disability Index (ODI) at the time of preoperation and during the last follow-up.ResultsAmong the 114 LDHR patients who obtained complete follow-up, fifty-four had anxiety/depression symptoms before surgery, which accounted for a incidence of 47%. Both Group A and Group B patients showed significant improvement in all evaluation indicators after PTED, but the overall prognosis of Group A was worse than that of Group B.ConclusionPTED can effectively improve patients’ pain, functional activities and mental health, which has a positive impact on patients’ quality of life, and there is a significant correlation between patients’ preoperative mental health and prognosis.

Chimeric antigen receptor T (CAR-T) cell therapy is a new treatment for cancers, but reports on curing immune-related skin diseases are limited. We report a case of successful CAR-T-cell therapy in a patient with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) who was incidentally cured of chronic generalized plaque psoriasis. The patient, a 65-year-old male who had a known history of psoriasis for 45 years, did not receive immunotherapy for psoriasis during this period. Imaging, molecular biology and immunology diagnostics confirmed DLBCL. After several weeks of standard-dose R-CHOP chemotherapy, the patient achieved partial remission, but according to CT, the patient relapsed, and there was no significant improvement in her psoriasis symptoms. Subsequently, the patient was enrolled in the CD19 CAR-T-cell therapy group. Four weeks after CAR-T-cell infusion, the patient’s abdominal pain disappeared, and there was a significant improvement in overall skin lesions. One year later, follow-up results indicated complete remission of R/R DLBCL (confirmed by PET-CT), with only minimal residual psoriatic skin lesions limited to the patient’s neck. The results of using CAR-T-cell therapy to achieve an incidental cure for psoriasis highlight the potential for exploring cell-based therapies for complex autoinflammatory skin diseases.

Abstract The waste of resources associated with fruit decay is rapidly spreading globally, threatening the interests of relevant practitioners and the health of consumer groups, and demanding precise solutions. Controlling fruit ripening through ethylene regulation is one of the most important strategies for providing high‐quality fruits. However, current materials for ethylene regulation still have difficulty realizing their application potential due to high manufacturing costs and performance deficiencies. In this review, the ethylene‐controlled release materials for ripening based on molecular encapsulation and the ethylene scavengers for preservation based on mechanisms such as oxidation, photodegradation, and adsorption are presented. We discuss and analyze a wide range of materials in terms of mechanism, performance, potential of applicability, and sustainability. The ethylene release behavior of encapsulating materials depends on the form in which the ethylene binds to the material as well as on environmental factors (humidity and temperature). For ethylene scavengers, there are a variety of scavenging mechanisms, but they generally require porous materials as adsorption carriers. We highlight the great opportunity of designing soft crystalline porous materials as efficient ethylene adsorbent due to their unique structural properties. We present this review, including a summary of practical characteristics and deficiencies of various materials, to establish a systematic understanding of fruit quality assurance materials applied to ethylene regulation, anticipating a promising prospect for these new materials.

Landslide risk assessment in coal mining economic cities faces challenges due to inadequate knowledge of indicator systems and modeling techniques, despite its crucial significance in geological disaster management. This study addresses this gap by proposing a novel framework encompassing data preparation, susceptibility analysis, consequence analysis, and final risk assessment. The primary objective is to reduce the complexity and inherent uncertainties associated with landslide risk assessment in these specific urban environments. First, two comprehensive databases for the indication system were established. One database focuses on landslide susceptibility, considering the region’s mining disturbances and disaster-prone environments. The other evaluates the effect of consequences while accounting for the pertinent risk variables. Second, a hybrid machine learning model called Geo-FR-SVM was developed by combining the GeoDetector, Frequency Ratio method, and Support Vector Machine model to improve landslide susceptibility mapping. Integrating the susceptibility map with the consequence map created using fuzzy set theory and fuzzy analytical hierarchy process methodologies resulted in the final landslide risk map. Our analysis revealed that elevation, distance to rivers and roads, groundwater level, and coal mining subsidence were the key factors influencing landslide occurrence in the Xishan mine area. The majority of the study area exhibits low landslide risk. However, higher consequence zones were primarily concentrated in highly populated residential regions and coal mine industrial zones in the east-central and western urban areas. Additionally, they are mainly distributed along the roads in the center region. With comparatively large percentages of landslide high-risk and extremely high-risk regions (4.596%, 3.855%, 3.625%, and 3.188%, respectively) at Tunlan Mine, Xiqu Mine, Zhenchengdi Mine, and Baijiazhuang Mine, these findings highlight the need for these mines to prioritize potential landslide identification and risk mitigation strategies. This framework offers broad applicability to other coal mining economic cities, serving as a valuable foundation for landslide risk management decision-making.

ObjectivesTo explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE).MethodsThis study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF).ResultsCompared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p

BackgroundNovel β-lactam antibiotics as well as other kinds of antibiotics have been used to treat complicated urinary tract infections (cUTIs); however, their efficacy and safety remain controversial.ObjectiveWe conducted a systematic review with meta-analysis to explore the efficacy and safety of novel β-lactam antibiotics versus other antibiotics against cUTIs.MethodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched systematically from inception through 15 March 2024 for clinical trials comparing novel β-lactam antibiotics with other antibiotics for treatment of cUTIs. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of clinical response, microbiologic response, adverse effects (AEs), serious adverse effects (SAEs). The quality of evidence was evaluated with the Cochrane Risk of Bias assessment tool. The review was registered in INPLASY (INPLASY202440054).ResultsTen randomized controlled trials involving 5, 925 patients met our inclusion criteria. Our meta-analysis revealed that there was no significant difference in overall clinical response (RR = 1.02), AEs (RR = 1.07), SAEs (RR = 1.20) between novel β-lactam antibiotics groups and other antibiotics groups. However, a significant difference was found in a subgroup of clinical cure rates at the end of treatment between novel β-lactam antibiotics groups and carbapenems groups, with low heterogeneity (RR = 1.02). A significant difference was observed in microbiologic response (RR = 1.11). Subgroup analysis revealed a significant difference in microbiologic response between novel BBL/BLS groups and carbapenems groups (RR = 1.13, I2 = 21%, P = 0.005). Differences was observed between novel BBL/BLS groups and piperacillin/tazobactam sodium groups (RR = 1.21, I2 = 70%, P = 0.02). Similar results were obtained from subgroup analysis of the difference in microbiologic response between novel β-lactam antibiotics groups and ertapenem groups (RR = 0.92, I2 = 0, P = 0.01).ConclusionNovel β-lactam antibiotics had similar overall clinical cure, AEs, SAE, to other antibiotics in the treatment of cUTIs. However, novel β-lactam antibiotics demonstrated superior clinical cure rates compared to carbapenems in a subgroup analysis, and exhibited better microbiologic response than other antibiotics.

Summary: Rooftop photovoltaics (RPVs) are crucial for decarbonizing the power sector and achieving carbon neutrality, with expected future capacity increases. The growth of RPVs necessitates substantial aluminum (Al) resources, contributing significantly to carbon dioxide (CO2) emissions from Al production. Given China’s bauxite shortage, recycling Al from waste RPV panels presents an effective solution to enhance resource security and mitigate CO2 emissions. We developed a framework to project waste RPV quantities and assess the recycling potential of Al and its impact on CO2 emissions from 2020 to 2060. Our findings indicate potential waste flows of 95–221 million tonnes (Mt) and recycled Al ranging from 5 to 28 Mt, with a primary Al supply gap of 25–43 Mt. Recycling could reduce CO2 emissions by 35–207 Mt over the period. This research underscores the importance of Al resource security and sustainable RPV industry development in China’s pursuit of carbon neutrality.

The influences of phase coarsening and loading direction on the ductility of Ni-based superalloys with phase coarsening are investigated, and the relationship between their microstructural and macroscopic mechanical properties is also explored in detail. It is found that the precipitation phase and the corresponding phase coarsening significantly influence the ductility of alloys. Furthermore, anisotropic features in ductility are observed after phase coarsening. Generally, as the volume fraction of precipitation particles or the degree of phase coarsening increases, the ductility of alloys gradually decreases; and it initially increases and then decreases gradually with the increase of loading angle, presenting an inverted ‘V’ shape. Comparatively, for the alloys with lower volume fraction of precipitation particles and higher degree of phase coarsening, the ductility shows different variation trends with the degree of phase coarsening and loading angle compared with that in materials with other microstructure features, taking the minimum value at the loading angle of 45°. The variations of ductility are closely connected to the characteristics of precipitate shape, size and distribution. The microstructure evolution and the loading direction significantly affect the initiation and movement of dislocations within the material, and result in various macroscopic ductility characteristics in the Ni-based superalloys.

ObjectiveLevosimendan and Sacubitril/Valsartan are both potent pharmacotherapeutic agents in the clinical management of heart failure characterized by reduced ejection fraction. However, the limited efficacy of monotherapy and the lack of extensive clinical experience with combination therapy necessitate further investigation. This study aimed to evaluate the therapeutic effects of combining levosimendan with sacubitril/valsartan on chronic heart failure with reduced ejection fraction, specifically through a meta-analysis of studies conducted in China.MethodsCochrane systematic evaluation method was used to complete data retrieval from the following related databases: (1) Wanfang database; (2) CNKI China Academic Journal Network; (3) Wipo Full-text Database of Chinese Sci-tech journals; (4) PubMed; (5) Medline; (6) Chinese Biomedical Literature Database; (7) Web of Science; and (8) Google Scholar database. We searched for studies published up to December 2021. Data were extracted from applicable articles. Meta-analyses were performed to assess the left ventricular ejection fractions (LVEF) level, NT-proBNP level, Clinical efficacy, and the left ventricular end-diastolic dimension (LVEDD) level outcomes, following PRISMA 2020 guidelines.ResultsA total of five randomized controlled trials (RCTs) comprising 398 patients were included, half of the patients for levosimendan combined with Sacubitril/Valsartan and half of the patients for control groups. The effective rate in experimental group was significantly higher than that in control group [Peto-OR = 3.08, 95% CI (1.83, 5.19), P

ABSTRACT Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens.IMPORTANCEOur study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

ABSTRACT Microbiomes play crucial roles in insect adaptation, especially under stress such as pathogen invasion. Yet, how beneficial microbiomes assemble remains unclear. The wood-boring beetle Monochamus alternatus, a major pest and vector of the pine wilt disease (PWD) nematode, offers a unique model. We conducted controlled experiments using amplicon sequencing (16S rRNA and ITS) within galleries where beetles and microbes interact. PWD significantly altered bacterial and fungal communities, suggesting distinct assembly processes. Deterministic factors like priority effects, host selection, and microbial interactions shaped microbiome composition, distinguishing healthy from PWN-infected galleries. Actinobacteria, Firmicutes, and Ophiostomataceae emerged as potentially beneficial, aiding beetle’s development and pathogen resistance. This study unveils how nematode-induced changes in gallery microbiomes influence beetle’s development, shedding light on microbiome assembly amid insect-pathogen interactions. Insights gleaned enhance understanding of PWD spread and suggest novel management strategies via microbiome manipulation.IMPORTANCEThis study explores the assembly process of gallery microbiomes associated with a wood-boring beetles, Monochamus alternatus, a vector of the pine wilt disease (PWD). By conducting controlled comparison experiments and employing amplicon approaches, the study reveals significant changes in taxonomic composition and functional adaptation of bacterial and fungal communities induced by PWD. It identifies deterministic processes, including priority effects, host selection, and microbial interactions, as major drivers in microbiome assembly. Additionally, the study highlights the presence of potentially beneficial microbes such as Actinobacteria, Firmicutes, and Ophiostomataceae, which could enhance beetle development and resistance to pathogens. These findings shed light on the intricate interplay among insects, microbiomes, and pathogens, contributing to a deeper understanding of PWD prevalence and suggesting innovative management strategies through microbiome manipulation.

ObjectiveThis study aimed to use visual mapping and bibliometric analysis to summarize valuable information on the tumor microenvironment (TME)-related research on hepatocellular carcinoma (HCC) in the past 20 years and to identify the research hotspots and trends in this field.MethodsWe screened all of the relevant literature on the TME of HCC in the Web of Science database from 2003 to 2023 and analysed the research hotspots and trends in this field via VOSviewer and CiteSpace.ResultsA total of 2,157 English studies were collected. According to the prediction, the number of papers that were published in the past three years will be approximately 1,394, accounting for 64.63%. China published the most papers (n=1,525) and had the highest total number of citations (n=32,253). Frontiers In Immunology published the most articles on the TME of HCC (n=75), whereas, Hepatology was the journal with the highest total number of citations (n=4,104) and average number of citations (n=91). The four clusters containing keywords such as “cancer-associated fibroblasts”, “hepatic stellate cells”, “immune cells”, “immunotherapy”, “combination therapy”, “landscape”, “immune infiltration”, and “heterogeneity” are currently hot research topics in this field. The keywords “cell death”, “ferroptosis”, “biomarkers”, and “prognostic features” have emerged relatively recently, and these research directions are becoming increasingly popular.ConclusionsWe identified four key areas of focus in the study of the TME in HCC: the main components and roles in the TME, immunotherapy, combination therapy, and the microenvironmental landscape. Moreover, the result of our study indicate that effect of ferroptosis on the TME in HCC may become a future research trend.

Arsenic (As) is a widespread global pollutant, and there is significant controversy surrounding its complex relationship with obesity, primarily focused on short-term exposure. Recognizing the prolonged nature of dietary arsenic exposure, this study involved feeding mice with arsenic-contained food for 14 months. The results showed that mice exposed to arsenic developed a non-alcoholic fatty liver condition, characterized by a light-yellow hue on the liver surface and various pathological alterations in the liver cells, including enlarged nuclei, cellular necrosis, inflammatory infiltration, dysfunctional mitochondria, and endoplasmic reticulum disorganization. There were also disruptions in biochemistry indices, with a significant increase in total cholesterol (TC) level and a decrease in high-density lipoprotein (HDL) level. However, some contradictory observations occurred, such as a significant decrease in body weight, triglyceride (TG) level, and the numbers of lipid droplets. Several genes related to lipid metabolism were tested, and a model was used to explain these discrepancies. Besides, examinations of the colon revealed compromised intestinal barrier function and signs of inflammation. Fecal 16S rRNA sequencing and pseudo-targeted metabolomics revealed disruptions in internal homeostasis, such as modules, nodes, connections, and lipid-related KEGG pathways. Fecal targeted metabolomics analyses of short-chain fatty acids (SCFAs) and bile acids (BAs) demonstrated a significant upregulation in three primary bile acids (CA, CDCA, TCDCA), four secondary bile acids (TUDCA, DCA, LCA, GUDCA), and total SCFAs level. Oxidative stress and inflammation were also evident. Additionally, based on correlation analysis and mediation analysis, it was assumed that changes in the microbiota (e.g., Dubosiella) can impact the liver metabolites (e.g., TGs) through alterations in fecal metabolites (e.g., LPCs). These findings provide a theoretical reference for the long-term effect of arsenic exposure on liver lipid metabolism.

The present study aimed to prepare polysaccharides from the pomace of Polygonatum rhizome and characterize their structural features and biological activities. After hot water extraction and DEAE-52 cellulose fractionation, a neutral polysaccharide (PKP) was obtained with 91.85% sugars and 0.45% proteins. Structural characterization indicated that PKP contained a main fraction with a molecular weight of 4.634 × 103 Da and was composed of →1)-β-D-Fruf-(2→ and →6)-β-D-Fruf-(2→ residues. PKP was a semi-crystalline polymer, and the Congo red assay suggested the presence of triple-helix structure in PKP. PKP exhibited moderate radical scavenging activity (including 15.55% inhibition of DPPH, 21.48% inhibition of ABTS, and 22.52% inhibition of ·OH) and could effectively protect MRC-5 cells from H2O2-induced oxidative damage at 0.01 mg/mL through inhibiting apoptosis, decreasing SA-β-galactosidase activity, and downregulating the expression levels of p16 and p53. Therefore, PKP could be used in functional foods and pharmaceuticals as an antioxidant. This study provides an attractive method for utilizing polysaccharides from waste materials.

Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.

Introduction Tuberculosis (TB) is a major global health issue, particularly, in India and South Africa. We aim to evaluate the potential of the new TB vaccine, Vaccae, to enhance TB control by integrating with active case finding (ACF) strategies in these regions.Methods Using age-structured dynamic models, we projected the epidemiological and economic outcomes of combining Vaccae vaccination with ACF over 27 years. In India, four age-targeted strategies were analysed: (1) adolescent (15 years), (2) adolescent and young adult (AYA, 15–34 years), (3) adult (18–55 years) and (4) elderly (60+ years). In South Africa, strategies were based on HIV status: (1) HIV-targeted, (2) non-HIV and (3) general population. The vaccine efficacy of Vaccae was set at 54.7%, priced at US$120 per course. Outcomes measured included reductions in TB incidence and mortality, prioritised based on budget, incremental cost-effectiveness ratios (ICER) and benefit-cost ratios (BCR).Results In India, the adult strategy could prevent 8.70 (95% UI: 6.86–11.13) million TB cases and 0.61 (0.39–0.91) million deaths, reducing incidence and mortality by 20.1% (18.7%–23.5%) and 19.0% (17.5%–22.5%), respectively. In South Africa, the general population strategy could avert 0.67 (0.45–0.99) million TB cases and 0.21 (0.15–0.28) million deaths, reducing incidence by 28.1% (26.1%–30.3%) and mortality by 27.0% (23.5%–30.0%). The vaccination budgets for the AYA strategy in India and the HIV-targeted strategy in South Africa were US$14.0 (10.14–23.29) billion and US$0.09 (0.06–0.15) billion, respectively. The ICERs were US$1082 (927–1426) and US$70 (53–123) per disability-adjusted life year averted, and the BCRs were 2.0 (1.6–2.4) and 176 (83.4–255.3), respectively. Thus, the AYA strategy in India and the HIV-targeted strategy in South Africa were the most favourable.Conclusion Integrating Vaccae vaccination with ACF could significantly enhance TB control in high-burden countries. Policymakers should consider these strategies, with further research needed to confirm the findings.

Abstract Extraction of U(VI) in water is of great significance in energy and environmental fields. However, the traditional methods usually fail due to the indispensable extra addition of catalyst, adsorbent, precipitant, or sacrificial agents, which may lead to enhanced extraction costs and secondary pollution. Here, a new efficient uranium extraction strategy is proposed based on triboelectricity without adding a catalyst or other additives. It is found only under the friction between the microbubbles (generated under ultrasonication) and the water flow, that reactive oxygen species (ROS) can largely be generated, which thus contributes to the solidification of U(VI) from water. In addition, the magnetic field can affect the phase of the product. Under mechanical stirring, the product contains (UO2)O2·2H2O, while which contains UO2(OH)2 and (UO2)O2·4H2O under the magnetic stirring. Quenching experiments are also carried out to explore the influence of environmental factors. Most importantly, it shows great potential in the extraction of U(VI) from seawater. This work proposes a catalyst‐free and light‐free strategy toward the solidification of U(VI) from water, which avoids the secondary pollution of the catalyst to the environment and is low‐cost, and has great potential in the real application.

We conducted a study on the surface compound modification of shot peening and pure carbon DLC coating to simultaneously meet the requirements of wear resistance and fatigue resistance of spline structure. The effects of surface compound modification were investigated on the surface morphology, residual stress profile, microstructure, and nano-indentation hardness of 16Cr3NiWMovNbE gear steel, and conducted a comparative study on fatigue performance. The results show that the surface compound modification inherits the surface morphology and compressive residual stress gradient of shot peening, while the surface residual stress is slightly smaller than that of shot peening. In addition, surface compound modification still reflects the characteristics of high hardness and high fracture resistance of DLC coatings. Under the bending load based on spline tooth root, compared to the original specimen, the fatigue life after shot peening, pure carbon DLC coating, and surface compound modification is increased by 3.68, 2.35, and 3.36 respectively. Although the compound modified surface still maintains the shot peening morphology with a increasing surface roughness and stress concentration coefficient, the 100 μm-depth compressive residual stress profile and the subgrain refinement layer introduced, as well as the hard surface layer with good load-bearing capacity, have played the role of fatigue strengthening.

Abstract Photonic crystals are a new class of optical microstructure materials characterized by a dielectric constant that varies periodically with space and features a photonic bandgap. Inspired by natural photonic crystals such as butterfly scales, a series of artificial photonic crystals are developed for use in integrated photonic platforms, biosensing, communication, and other fields. Among them, colloidal photonic crystals (CPCs) have gained widespread attention due to their excellent optical properties and advantages, such as ease of preparation and functionalization. This work reviews the classification and self‐assembly principles of CPCs, details some of the latest biomedical applications of large‐area, high‐quality CPCs prepared using advanced self‐assembly methods, summarizes the existing challenges in CPC construction and application, and anticipates future development directions and optimization strategy. With further advancements, CPCs are expected to play a more critical role in biosensors, drug delivery, cell research, and other fields, bringing significant benefits to biomedical research and clinical practice.

BackgroundMedical health workers play an essential role in the healthcare system and face unique workplace stressors. However, the impact of psychological stress on their physical health has received less attention compared to the general population.MethodsWe retrospectively analyzed the Self-rating Depression Scale (SDS) questionnaires and blood testing results from 1963 medical health workers. Multivariate linear regression analysis using a backward stepwise selection strategy to identify physical examination indicators that were significantly affected by depression.ResultsDepression severity, as measured by SDS index score, was positively correlated with the levels of hemoglobin (coefficient 0.0027, p = 0.0412), platelet count (coefficient 0.0005, p = 0.0198), and uric acid (coefficient 0.0004, p = 0.0492), while negatively correlated with red blood cell count (coefficient-0.0895, p = 0.0406). Similar results were observed in the subgroup analysis stratified by age and sex.ConclusionOur study found a significant association between higher levels of depression and specific physiological indicators in healthcare professionals, including elevated hemoglobin, platelet counts, and uric acid levels, as well as decreased red blood cell counts. These changes in blood parameters may reflect underlying physiological stress and inflammation, potentially increasing overall health risks for healthcare workers. Addressing these physiological changes may be crucial for mitigating the health risks associated with depression. To validate our findings and develop targeted interventions, larger multi-center studies are needed to further explore the relationship between depression severity and blood parameters in healthcare professionals.

Abstract Genomics allows the tracing of origin and evolution of cancer at molecular scale and underpin modern cancer diagnosis and treatment systems. Yet, molecular biomarker‐guided clinical decision‐making encounters major challenges in the realm of individualized medicine, consisting of the invasiveness of procedures and the sampling errors due to high tumor heterogeneity. By contrast, medical imaging enables noninvasive and global characterization of tumors at a low cost. In recent years, radiomics has overcomes the limitations of human visual evaluation by high‐throughput quantitative analysis, enabling the comprehensive utilization of the vast amount of information underlying radiological images. The cross‐scale integration of radiomics and genomics (hereafter radiogenomics) has the enormous potential to enhance cancer decoding and act as a catalyst for digital precision medicine. Herein, we provide a comprehensive overview of the current framework and potential clinical applications of radiogenomics in patient care. We also highlight recent research advances to illustrate how radiogenomics can address common clinical problems in solid tumors such as breast cancer, lung cancer, and glioma. Finally, we analyze existing literature to outline challenges and propose solutions, while also identifying future research pathways. We believe that the perspectives shared in this survey will provide a valuable guide for researchers in the realm of radiogenomics aiming to advance precision oncology.

BackgroundFor patients with metastatic upper tract urothelial carcinoma (UTUC), the preferred first-line treatment is platinum-based chemotherapy. Immunotherapy can be considered a subsequent treatment if the chemotherapy is ineffective or the disease progresses. However, how should treatment be administered if immunotherapy is useless and the patient cannot take chemotherapy? Especially in patients who have metastasized after radical nephroureterectomy (RNU).Case presentationA 68-year-old woman was admitted to the hospital due to left flank pain for two weeks and was diagnosed with metastatic UTUC after RNU. The patient underwent systemic chemotherapy with gemcitabine and cisplatin (GC), as well as reduced-dose GC, but developed myelosuppression. Immunotherapy was ineffective, so Disitamab vedotin (RC48) was chosen.ResultsDisitamab vedotin (RC48) monotherapy was administered for 13 cycles, during which thyroid function remained normal, the patient responded well to the treatment, and the disease was controlled well. In the subsequent two years of follow-up, there was no disease recurrence.ConclusionThe long-term treatment regimen with RC48 is feasible for metastatic UTUC after RNU, and RC48 monotherapy is suitable as first-line therapy for selected patients.

BackgroundThe relationship between dietary selenium intake and sarcopenia remains poorly understood. Therefore, this study investigates the associations between dietary selenium intake and sarcopenia among American adults.MethodsThis cross-sectional study analyzed data from 19,696 participants in the National Health and Nutrition Examination Survey (NHANES) for the periods 1999–2006 and 2011–2018. Appendicular muscle mass, assessed using dual-energy x-ray absorptiometry and adjusted for body mass index, was used as a marker for sarcopenia. Dietary selenium intake was evaluated using the 24-h dietary recall system, and the study accounted for the complex sampling methodology and incorporated dietary sample weights in the analysis.ResultsAmong the 19,696 participants, the prevalence of sarcopenia was found to be 8.46%. When compared to the lowest quintile of dietary selenium intake (Q1, < 80.10 μg/day), the odds ratios for sarcopenia in the second quintile (Q2, 80.10–124.61 μg/day) and the third quintile (Q3, >124.61 μg/day) were 0.80 [95% confidence interval (CI): 0.70–0.92, p = 0.002] and 0.61 (95% CI: 0.51–0.73, p < 0.001), respectively. A negative relationship was observed between dietary selenium intake and sarcopenia (non-linear: p = 0.285). Furthermore, sensitivity analyses revealed a robust association between selenium intake and the prevalence of sarcopenia after further adjusting for blood selenium levels.ConclusionThe results suggest an inverse association between dietary selenium intake and the prevalence of sarcopenia among American adults.

IntroductionGrazer exclosure is widely regarded as an effective measure for restoring degraded grasslands, having positive effects on soil microbial diversity. The Intergovernmental Panel on Climate Change (IPCC) predicts that global surface temperatures will increase by 1.5–4.5°C by the end of the 21st century, which may affect restoration practices for degraded grasslands. This inevitability highlights the urgent need to study the effect of temperature on grassland soil microbial communities, given their critical ecological functions.MethodsHere, we assessed the effects of heavy grazing (control), grazer exclosure, and grazer exclosure plus warming by 1.5°C on soil microbial community diversity and network properties as well as their relationships to soil physicochemical properties.Results and discussionOur results showed that grazer closure increased soil microbial richness relative to heavy grazing controls. Specifically, bacterial richness increased by 7.9%, fungal richness increased by 20.2%, and the number of fungal network nodes and edges increased without altering network complexity and stability. By contrast, grazer exclosure plus warming decreased bacterial richness by 9.2% and network complexity by 12.4% compared to heavy grazing controls, while increasing fungal network complexity by 25.8%. Grazer exclosure without warming increased soil ammonium nitrogen content, while warming increased soil nitrate nitrogen content. Soil pH and organic carbon were not affected by either exclosure strategy, but nitrate nitrogen was the dominant soil factor explaining changes in bacterial communities.ConclusionOur findings show that grazer exclosure increases soil microbial diversity which are effective soil restoration measures for degraded desert steppe, but this effect is weakened under warming conditions. Thus, global climate change should be considered when formulating restoration measures for degraded grasslands.

BackgroundLimbic structures have recently garnered increased attention in Parkinson’s disease (PD) research. This study aims to explore changes at the whole-brain level in the structural network, specifically the white matter fibres connecting the thalamus and limbic system, and their correlation with the clinical characteristics of patients with PD.MethodsBetween December 2020 and November 2021, we prospectively enrolled 42 patients with PD and healthy controls at the movement disorder centre. All participants underwent diffusion tensor imaging (DTI), 3D T1-weighted imaging (3D-T1WI), and routine brain magnetic resonance imaging on a 3.0 T MR scanner. We employed the tract-based spatial statistical (TBSS) analytic approach, examined structural network properties, and conducted probabilistic fibre tractography to identify alterations in white matter pathways and the topological organisation associated with PD.ResultsIn patients with PD, significant changes were observed in the fibrous tracts of the prefrontal lobe, corpus callosum, and thalamus. Notably, the fibrous tracts in the prefrontal lobe and corpus callosum showed a moderate negative correlation with the Freezing of Gait Questionnaire (FOG-Q) scores (r = −0.423, p = 0.011). The hippocampus and orbitofrontal gyrus exhibited more fibre bundle parameter changes than other limbic structures. The mean streamline length between the thalamus and the orbitofrontal gyrus demonstrated a moderate negative correlation with Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III (r = −0.435, p = 0.006). Topological parameters, including characteristic path length (Lp), global efficiency (Eg), normalised shortest path length (λ) and nodal local efficiency (Nle), correlated moderately with the MDS-UPDRS, HAMA, MoCA, PDQ-39, and FOG-Q, respectively.ConclusionDTI is a valuable tool for detecting changes in water molecule dispersion and the topological structure of the brain in patients with PD. The thalamus may play a significant role in the gait abnormalities observed in PD.

Plant-associated microbial communities are crucial for plant growth and health. However, assembly mechanisms of microbial communities and microbial interaction patterns remain elusive across vary degrees of pathogen-induced diseases. By using 16S rRNA high-throughput sequencing technology, we investigated the impact of wildfire disease on the microbial composition and interaction network in plant three different compartments. The results showed that pathogen infection significantly affect the phyllosphere and rhizosphere microbial community. We found that the primary sources of microbial communities in healthy and mildly infected plants were from the phyllosphere and hydroponic solution community. Mutual exchanges between phyllosphere and rhizosphere communities were observed, but microbial species migration from the leaf to the root was rarely observed in severely infected plants. Moreover, wildfire disease reduced the diversity and network complexity of plant microbial communities. Interactions among pathogenic bacterial members suggested that Caulobacter and Bosea might be crucial “pathogen antagonists” inhibiting the spread of wildfire disease. Our study provides deep insights into plant pathoecology, which is helpful for the development of novel strategies for phyllosphere disease prediction or prevention.

Background and objectives: Exosomes, which are small nanoscale vesicles capable of secretion, have garnered significant attention in recent years because of their therapeutic potential, particularly in the context of kidney diseases. Notably, human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) are emerging as promising targeted therapies for renal conditions. The aim of this study was to investigate the therapeutic effects of hucMSC-Exos on diabetic kidney disease (DKD) both in vivo and in vitro. Additionally, this study seeks to elucidate cellular and molecular differentials, as well as the expression of relevant signaling pathways, through single-cell RNA sequencing. This endeavor was designed to enhance our understanding of the connection between hucMSC-Exos and the pathogenesis of DKD. Methods and results: The study commenced with the extraction and characterization of hucMSC-Exos, including the determination of their concentrations. Animal experiments were conducted to evaluate the therapeutic potential of hucMSC-Exos in a DKD mouse model. Subsequently, single-cell sequencing was employed to investigate the molecular mechanisms underlying the efficacy of extracellular vesicles in ameliorating DKD. These findings were further substantiated by cell-based experiments. Importantly, the results indicate that hucMSC-Exos can impede the progression of DKD in mice, with macrophage activation playing a pivotal role in this process. Conclusions: The in vivo experiments conclusively established hucMSC-Exos as a pivotal component in preserving renal function and retarding the progression of DKD. Our utilization of single-cell sequencing technology, in conjunction with in vivo and in vitro experiments, provides compelling evidence that M2 macrophages are instrumental in enhancing the amelioration of diabetic nephropathy.

Summary: Integrins play critical roles in connecting the extracellular matrix and actin. While the upregulation of integrins is thought to promote cancer stemness and metastasis, the mechanisms underlying their upregulation in cancer stem cells (CSCs) remain poorly understood. Herein, we show that USP22 is essential in maintaining breast cancer cell stemness by promoting the transcription of integrin β1 (ITGB1). Both genetic and pharmacological inhibition of USP22 largely impaired breast CSCs self-renewal and prevented their metastasis. Reconstitution of integrin β1 partially rescued USP22-null breast cancer metastasis. USP22 functions as a bona fide deubiquitinase to protect the proteasomal degradation of the forkhead box M1 (FoxM1), a transcription factor for tumoral ITGB1 gene transcription. Immunohistochemistry staining detected a positive correlation among USP22, FoxM1, and integrin β1 in human breast cancers. Collectively, our study identifies the USP22-FoxM1-integrin β1 signaling axis as critical for cancer stemness and offers a potential target for antitumor therapy.