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Systemic lupus erythematosus (SLE) is a multi-organ and systemic autoimmune disease characterized by an imbalance of humoral and cellular immunity. The efficacy and side effects of traditional glucocorticoid and immunosuppressant therapy remain controversial. Recent studies have revealed abnormalities in mesenchymal stem cells (MSCs) in SLE, leading to the application of bone marrow-derived MSCs (BM-MSCs) transplantation technique for SLE treatment. However, autologous transplantation using BM-MSCs from SLE patients has shown suboptimal efficacy due to their dysfunction, while allogeneic mesenchymal stem cell transplantation (MSCT) still faces challenges, such as donor degeneration, genetic instability, and immune rejection. Therefore, exploring new sources of stem cells is crucial for overcoming these limitations in clinical applications. Human amniotic epithelial stem cells (hAESCs), derived from the eighth-day blastocyst, possess strong characteristics including good differentiation potential, immune tolerance with low antigen-presenting ability, and unique immune properties. Hence, hAESCs hold great promise for the treatment of not only SLE but also other autoimmune diseases.

IntroductionRespiratory viral infection (RVI) is of very concern after the outbreak of COVID-19, especially in pediatric departments. Learning pathogen spectrum of RVI in children previous the epidemic of COVID-19 could provide another perspective for understanding RVI under current situation and help to prepare for the post COVID-19 infection control.MethodsA nucleic acid sequence-based amplification (NASBA) assay, with 19 pairs of primers targeting various respiratory viruses, was used for multi-pathogen screening of viral infections in children presenting influenza-like illness (ILI) symptoms. Children with ILI at the outpatient department of Beijing Tsinghua Changgung Hospital during the influenza epidemic from 12/2018 to 01/2019 were included. Throat swabs were obtained for both the influenza rapid diagnostic test (IRDT) based on the colloidal gold immunochromatographic assay and the NASBA assay, targeting various respiratory viruses with an integrated chip technology.Results and discussionOf 519 patients, 430 (82.9%) were positive in the NASBA assay. The predominant viral pathogens were influenza A H1N1 pdm1/2009 (pH1N1) (48.4%) and influenza A (H3N2) (18.1%), followed by human metapneumovirus (hMPV) (8.8%) and respiratory syncytial virus (RSV) (6.1%). Of the 320 cases identified with influenza A by NASBA, only 128 (40.0%) were positive in the IRDT. The IRDT missed pH1N1 significantly more frequently than A (H3N2) (P

Gastric cancer is a type of digestive tract cancer with a high morbidity and mortality, which leads to a major health burden worldwide. More research into the functions of the immune system will improve therapy and survival in gastric cancer patients. We attempted to identify potential biomarkers or targets in gastric cancer via bioinformatical analysis approaches. Three gene expression profile datasets (GSE79973, GSE103236, and GSE118916) of gastric tissue samples were obtained from the Gene Expression Omnibus database. There were 65 overlapping differentially expressed genes (DEGs) identified from three microarrays. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway were carried out for the key functions and pathways enriched in the DEGs. Then, ten hub genes were identified by protein–protein interaction network. In addition, we observed that collagen type V alpha 2 (COL5A2) was linked to gastric cancer prognosis as well as M2 macrophage infiltration. Furthermore, COL5A2 enhanced gastric cancer cell proliferation through the PI3K-AKT signaling pathway and polarized M2 macrophage cells. Therefore, in this study, we found that COL5A2 was associated with the development of gastric cancer which might function as a potential therapeutic target for the disease.

ABSTRACTThe COVID-19 pandemic presents a major threat to global public health. Several lines of evidence have shown that the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), along with two other highly pathogenic coronaviruses, SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV) originated from bats. To prevent and control future coronavirus outbreaks, it is necessary to investigate the interspecies infection and pathogenicity risks of animal-related coronaviruses. Currently used infection models, including in vitro cell lines and in vivo animal models, fail to fully mimic the primary infection in human tissues. Here, we employed organoid technology as a promising new model for studying emerging pathogens and their pathogenic mechanisms. We investigated the key host-virus interaction patterns of five human coronaviruses (SARS-CoV-2 original strain, Omicron BA.1, MERS-CoV, HCoV-229E, and HCoV-OC43) in different human respiratory organoids. Five indicators, including cell tropism, invasion preference, replication activity, host response and virus-induced cell death, were developed to establish a comprehensive evaluation system to predict coronavirus interspecies infection and pathogenicity risks. Using this system, we further examined the pathogenicity and interspecies infection risks of three SARS-related coronaviruses (SARSr-CoV), including WIV1 and rRsSHC014S from bats, and MpCoV-GX from pangolins. Moreover, we found that cannabidiol, a non-psychoactive plant extract, exhibits significant inhibitory effects on various coronaviruses in human lung organoid. Cannabidiol significantly enhanced interferon-stimulated gene expression but reduced levels of inflammatory cytokines. In summary, our study established a reliable comprehensive evaluation system to analyse infection and pathogenicity patterns of zoonotic coronaviruses, which could aid in prevention and control of potentially emerging coronavirus diseases.

Background: Metabolic reprogramming is an important player in the prognosis of cancer patients. However, metabolism-related genes (MRGs) that are essential to the prognosis of bladder cancer (BLCA) are nor yet fully understood. The purpose of this study is to use bioinformatics methods to establish prognostic models based on MRGs in BLCA to screen potential biomarkers. Methods: Based on the transcriptomic data from BLCA patients in The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed genes related to metabolism and analyzed the functional enrichment by edgeR package. A prognostic model was generated using univariate Cox regression analysis and validated using GEO dataset. The prognostic risk model was analyzed by the Kaplan-Meier curve. The single cell RNA sequencing (scRNA-seq) revealed the gene interaction networks and traced the development trajectories of distinct cell lineages. The levels of key metabolism-related biomarkers in vitro were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We screened 201 differentially expressed metabolism-related genes (DEMRGs), which were significantly enriched in oxidative phosphorylation. The risk model was constructed by 5 biomarkers. qRT-PCR analysis verified that there is a significant higher expression of FASN and MTHFD1L in carcinoma tissue. Conclusions: This study constructed a novel prognostic model based on a combination of clinical and molecular factors that related to metabolic reprogramming, which has the potential to improve the prediction of independent prognosis indicators and management of BLCA patients, leading to better treatment outcomes and survival rates.

With the rapid development of urbanization, land use change has occurred in most karst mountain regions of North China over the last decade, so studying landscape pattern changes induced by urbanization would have implicational significance to regional planning and sustainability. Based on RS, GIS, and field investigation, land use change induced by urbanization in Jinan city belonging to the karst mountainous area of North China was analyzed over 30 years from 1987 to 2018, and further the landscape response of these changes was explored. The results indicate that (1) the most obvious changes have occurred in both urban/built-up land area and cropland area with rapid urbanization development in Jinan’s karst area, and the former increased by 246.4 km2 but the latter decreased by 343.3 km2 from 1987 to 2018; (2) landscape pattern of land use is profoundly changed by quick urbanization in the period from 2000 to 2018, but does not siginificently from 1987 to 2000; and (3) in the monitoring period, the cropland’s shape inclines to fragmentation and regularization, and the shapes of urban/built-up land and barren land have become increasingly distinct from the patch class level; from patch landscape level, the artificial landscape type (urban/built-up land) is increasingly dominant but the natural landscape type (grassland) is decreasingly dominant, thereby resulting in the disturbance of urban karst environment of Jinan city. Therefore, a protection policy should be taken to achieve strong urban karst sustainable development of North China.

To study the softening bending properties and mechanism of teakwood, it was extractively pretreated by using superheated steam, the triethanolamine compound was used as a softening solution, which was infiltrated into the wood by vacuum impregnation and synergistically softened through saturated steam to improve the bending properties of teakwood. Analysis by Fourier transform infrared spectroscopy (FTIR), Carbon 13 nuclear magnetic resonance (13C NMR), and X-ray photoelectron spectroscopy (XPS) showed that the synergistic softening treatment elevated the content of O and N elements in the softening solution and together with the C elements in the wood, formed C-NH2 and C-N bonds, which increased the molecular activity and improved the softening properties of teakwood. Scanning electron microscope (SEM) observations revealed that the outer conduits, cell walls, and fibrous tissue structures of the teakwood were stretched after softening and bending, and even microcracks of different degrees were formed between the cell walls. According to the load–deformation relationship of teakwood softening bending, the stress–strain relationship was theoretically derived and the bifold constitutive model of teakwood bending was constructed after fitting the constitutive relationship data, the integrated correlation coefficient R2 was 96.25%, which proved that the present model can better simulate the constitutive relationship of teakwood in bending.

The use of immune checkpoint inhibitors (ICIs) can improve survival of patients with malignant tumors, however, the ICI treatment is associated with unpredictable toxicity as immune-related adverse effects (irAEs). Here we report two cases of metastatic malignant gastrointestinal tumors where severe immune-mediated hepatotoxicity (IMH) developed, characterized by liver failure, after the ICI therapy. Through a strong immunosuppressive treatment and a non-biological artificial liver and supportive treatment, the liver function was restored in both cases, and the anti-tumor treatment effect was guaranteed. These results showed that the non-biological artificial liver could be capable of improve prognosis during the ICI therapy.

Rabies is a highly prevalent zoonotic disease and a public health threat worldwide. Currently licensed rabies vaccines are effective but less is known which would protect cattle. This study describes the construction of a novel recombinant bovine herpes virus type I (BHV-1) expressing rabies virus glycoprotein (RABV G) instead of its gE glycoprotein (gE) by CRISPR-Cas9 and homologous recombination technology (BHV-1-ΔgE-G). Insertion of the RABV G gene is stable after 20 rounds of in vitro passaging and the recombinant virus replicates to high titers in MDBK cells. The RABV G expresses in the recombinant virus-infected cells and on the virion surface of BHV-1-ΔgE-G. One single immunization with BHV-1-ΔgE-G-activated dendritic cells (DCs) and B cells furthermore induced a protective immune response in mice against severe lethal challenge infection. A protective level of RABV-specific virus-neutralizing antibody (VNA) was detected in intramuscular immunized mice and cattle without any clinical symptoms. This research demonstrated that the BHV-1 vector-based RABV vaccine is a potential candidate for cattle.

The classifications and reductions of radially symmetric diffusion system are studied due to the conditional Lie-Bäcklund symmetry method. We obtain the invariant condition, which is the so-called determining system and under which the radially symmetric diffusion system admits second-order conditional Lie-Bäcklund symmetries. The governing systems and the admitted second-order conditional Lie-Bäcklund symmetries are identified by solving the nonlinear determining system. Exact solutions of the resulting systems are constructed due to the compatibility of the original system and the admitted differential constraint corresponding to the invariant surface condition. For most of the cases, they are reduced to solving four-dimensional dynamical systems.

The sign-invariant theory is used to study the radially symmetric nonlinear diffusion equations with gradient-dependent diffusivities. The first-order non-stationary sign-invariants and the first-order non-autonomous sign-invariants admitted by the governing equations are identified. As a consequence, the exact solutions to the resulting equations are constructed due to the corresponding reductions. The phenomena of blow-up, extinction and behavior of some solutions are also described.

Jieduquyuziyin prescription (JP) has been used to treat systemic lupus erythematosus (SLE). Although the effectiveness of JP in the treatment of SLE has been clinically proven, the underlying mechanisms have yet to be completely understood. We observed the therapeutic actions of JP in MRL/lpr mice and their bone marrow-derived macrophages (BMDMs) and the potential mechanism of their inhibition of inflammatory activity. To estimate the effect of JP on suppressing inflammatory activity, BMDMs of MRL/lpr and MRL/MP mice were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. Among them, JP and its treated serum were subjected to quality control, and BMDMs were separated and identified. The results showed that in the JP group of BMDMs stimulated by Lipopolysaccharide (LPS) in MRL/lpr mice, the secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) reduced, and the expressions of Interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream nuclear factor κB (NF-κB) pathway decreased. Meanwhile, the alleviation of renal pathological damage, the decrease of urinary protein and serum anti-dsDNA contents, the inhibition of TNF-α level, and then the suppression of the IRAK1-NF-κB inflammatory signaling in the spleen and kidney, confirmed that the therapeutic effect of JP. These results demonstrated that JP could inhibit the inflammatory activity of MRL/lpr mice and their BMDMs by suppressing the activation of IRAK1-NF-κB signaling and was supposed to be a good choice for the treatment of SLE.

A conditional Lie-Bäcklund symmetry method and differential constraint method are developed to study the radially symmetric nonlinear convection-diffusion equations with source. The equations and the admitted conditional Lie-Bäcklund symmetries (differential constraints) are identified. As a consequence, symmetry reductions to two-dimensional dynamical systems of the resulting equations are derived due to the compatibility of the original equation and the additional differential constraint corresponding to the invariant surface equation of the admitted conditional Lie-Bäcklund symmetry.

The conditional Lie–Bäcklund symmetry method is applied to investigate the functionally generalized separation of variables for quasi-linear diffusion equations with a source. The equations and the admitted conditional Lie–Bäcklund symmetries related to invariant subspaces are identified. The exact solutions possessing the form of the functionally generalized separation of variables are constructed for the resulting equations due to the corresponding symmetry reductions.

Previous studies have shown that wild-type (wt) rabies virus (RABV) evades the host immune response by restricting expression of glycoprotein (G), which blocks activation of dendritic cells (DCs) and induces production of virus-neutralizing antibodies (VNAs). In the present study, wt RABVs not only restricted G expression but also reduced incorporation of G into mature virions compared with laboratory-adapted viruses. A recombinant RABV expressing triple G was used to further determine whether G expression relates to incorporation. The recombinant virus showed higher expression and incorporation of G and activated more DCs than the virus that expressed a single copy of G. Removal of G from viruses using subtilisin or Dithiothreitol (DTT)/ Nonidet P-40 (NP40) almost completely abolishes DC activation and VNA production. Consequently, these G-depleted viruses cause lethal infection in mice. Thus, wt RABVs can subvert DC-induced antiviral immune response and maintain pathogenicity by decreasing G expression in infected cells and G incorporation into virions.

Following a constituent enrichment step on a silica gel column, four phenyl-ethanoid glycosides were successfully isolated from Cistanches deserticola and purified by preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of ethyl acetate-n-butanol-ethanol-water (40:6:6:50, v/v/v/v). A total of 30.9 mg acteoside, 13.0 mg isoacteoside, 12.5 mg syringalide A 3'-α-L-rhamnopyranoside and 7.2 mg 2'-acetylacteoside with purity of higher than 95%, as determined by HPLC-ELSD, were obtained in one-step separation from 297 mg of Cistanche deserticola extract, respectively. Their structures were identified by HR-MS, 1H-NMR and 13C-NMR.

Autism is a neurodevelopmental disorder with unknown etiology. In some cases, typically developing children regress into clinical symptoms of autism, a condition known as regressive autism. Protein kinases are essential for G-protein-coupled receptor-mediated signal transduction, and are involved in neuronal functions, gene expression, memory, and cell differentiation. Recently, we reported decreased activity of protein kinase A (PKA) in the frontal cortex of subjects with regressive autism. In the present study, we analyzed the activity of protein kinase C (PKC) in the cerebellum and different regions of cerebral cortex from subjects with regressive autism, autistic subjects without clinical history of regression, and age-matched control subjects. In the frontal cortex of subjects with regressive autism, PKC activity was significantly decreased by 57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as compared to non-regressed autistic subjects (p = 0.0048). PKC activity was unaffected in the temporal, parietal and occipital cortices, and in the cerebellum in both autism groups, i.e., regressive and non-regressed autism as compared to control subjects. These results suggest brain region-specific alteration of PKC activity in the frontal cortex of subjects with regressive autism. Further studies showed a negative correlation between PKC activity and restrictive, repetitive and stereotyped pattern of behavior (r= -0.084, p = 0.0363) in autistic individuals, suggesting involvement of PKC in behavioral abnormalities in autism. These findings suggest that regression in autism may be attributed, in part, to alterations in G-protein-coupled receptor-mediated signal transduction involving PKA and PKC in the frontal cortex.

The radially symmetric nonlinear reaction–diffusion equation with gradient-dependent diffusivity is investigated. We obtain conditions under which the equations admit second-order conditional Lie–Bäcklund symmetries and first-order Hamilton–Jacobi sign-invariants which preserve both signs (≥0 and ≤0) on the solution manifold. The corresponding reductions of the resulting equations are established due to the compatibility of the invariant surface conditions and the governing equations.

The method of linear determining equations is constructed to study conditional Lie–Bäcklund symmetry and the differential constraint of a two-component second-order evolution system, which generalize the determining equations used in the search for classical Lie symmetry. As an application of the approach, the two-component reaction-diffusion system with power diffusivities is considered. The conditional Lie–Bäcklund symmetries and differential constraints admitted by the reaction-diffusion system are identified. Consequently, the reductions of the resulting system are established due to the compatibility of the corresponding invariant surface conditions and the original system.

Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP-dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.

Abstract Background Currently, the synthesis pathway of metal nuclide-labeled radiopharmaceuticals is mainly divided into two steps: first, connecting the chelator with the target molecule, and second, labeling the metal nuclide to the chelator. However, the second step of the reaction to label the metal nuclide requires high temperature (90–100 °C), which tends to denature and inactivate the target molecule, leading to loss of biological activities, especially the targeting ability. A feasible solution may be the click chemistry labeling method, which consists of reacting a metal nuclide with a chelating agent to generate an intermediate and then synthesizing a radiopharmaceutical agent via the click chemistry intermediate and the target molecule-alkyne compound. In this study, through the click chemistry of 177Lu-DOTA-N3 with prostate-specific membrane antigen (PSMA)-alkyne compound, 177Lu-labeled PSMA-targeted molecular probe was synthesized and evaluated for its potential to be cleared from the bloodstream and rapidly distributed to tissues and organs, achieving a high target/non-target ratio. 177Lu-PSMA-617 was utilized as an analogue for comparison in terms of synthesizing efficiency and PSMA-targeting ability. Results A novel 177Lu-labeled PSMA radioligand was successfully synthesized through the click chemistry of 177Lu-DOTA-N3 with PSMA-alkyne compound, and abbreviated as 177Lu-DOTA-CC-PSMA, achieving a radiochemical yield of 77.07% ± 0.03% (n = 6) and a radiochemical purity of 97.62% ± 1.49% (n = 6) when purified by SepPak C18 column. Notably, 177Lu-DOTA-CC-PSMA was characterized as a hydrophilic compound that exhibited stability at room temperature and commendable pharmacokinetic properties, such as the superior uptake (19.75 ± 3.02%ID/g at 0.5 h) and retention (9.14 ± 3.16%ID/g at 24 h) within xenografts of 22Rv1 tumor-bearing mice. SPECT/CT imaging indicated that radioactivity in both kidneys and bladder was essentially eliminated after 24 h, while 177Lu-DOTA-CC-PSMA was further enriched and retained in PSMA-expressing tumors, resulting in the high target/non-target ratio. Conclusion This study demonstrated the potential of click chemistry to unify the synthesis of metal radiopharmaceuticals, and 177Lu-DOTA-CC-PSMA was found for rapid clearance and appropriate chemical stability as a PSMA-targeted radioligand.

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues. Graphical Abstract

Objective To investigate the efficacy and safety of a Compound Acid in improving seborrheic dermatitis of the scalp. Methods Fifty patients with seborrheic dermatitis who met the inclusion criteria were enrolled. The subjects underwent scalp brushing with Compound Acid for a total of four brushings, with the first acid brushing on the day of enrollment and subsequent brushings at one-week interval. Symptom scores were assessed before each acid brushing. A follow-up examination was conducted two weeks after the last acid brushing. Clinical signs and symptoms such as papules, greasiness, erythema, and dandruff were scored using skin microscopy. The status of Malassezia infection was detected using fungus fluorescent microscope. A questionnaire was used to evaluate subjects' scalp itching and pain. Results Forty-seven subjects completed this study. Following the use of the Compound Acid, subjects showed significant improvements in maculopapule scores (from 2.09±1.25 to 0.13±0.34), greasiness scores (from 3.19±0.77 to 0.87±0.65), erythema scores (from 3.23±0.63 to 0.43±0.68), and dandruff scores (from 3.26±0.94 to 0.55±0.65) (all P

In order to investigate the functional effects of superfine grinding technology on Zanthoxylum bungeanum seed, in this study, superfine grinding technology was used to prepare Zanthoxylum bungeanum superfine powder. The basic components, particle size, color, surface morphology, and the water/oil holding capacity, expansion force, compaction density were investigated and recorded using particle size analyzer, spectrophotometer, and scanning electron microscope (SEM). The results showed that the soluble dietary fiber content of Zanthoxylum bungeanum seed powder gradually increased with the decrease of particle size. In comparison with the conventionally produced powder, the size of superfine powder could decrease to 7.69 μm, along with a larger specific surface area and stronger powder uniformity. As the particle size decreased, the color of the superfine powder gradually increased in L*, a*, and b* values. After superfine grinding, the water-holing capacity, oil-holding capacity, and swelling capacity would increase to 1.65 g/g, 1.16 g/g, and 2.35 mL/g, respectively. In addition, angles of repose and slide increased butthe tap density exhibited the opposite tendency. SEM images revealed that fiber bundle could be more thoroughly crushed with grinding time. In summary, the uniform Zanthoxylum bungeanum seed powder with a smaller particle size, higher powder uniformity, more soluble dietary fiber and better hydration capacity can be prepared through superfine grinding. However, to some extent, superfine grinding will also decrease the density and fluidity of Zanthoxylum bungeanum seed powder.

Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.

Background: Remote ischemic conditioning (RIC) is considered a promising non-pharmacological therapeutic strategy to mitigate ischemic injury. Although the precise mechanisms of RIC's protective effects remain elusive, existing data suggest that exosomes contribute significantly to these processes through cell-to-cell communication Objective: This review aims to elucidate the role of exosomes in RIC-mediated multi-organ protection. Methods: We systematically searched multiple databases through October 2023 for preclinical studies evaluating the effect of exosomes in ischemic models using RIC procedures. Key outcomes, such as improved organ function and reduced infarct size, were recorded. Articles were selected and data were extracted by independent pairs of reviewers. Findings: A total of 16 relevant studies were identified in this review, showing that circulating exosomes derived from the plasma of RIC-treated animals exhibited protective effects akin to those of the RIC procedure itself. Exosome concentrations were measured in eight studies, six of which reported significant increases in the RIC group. Additional findings indicated that RIC might primarily modulate the expression of miRNAs and bioactive molecules delivered by exosomes, rather than directly altering circulating exosome levels. Notably, the expression of 11 distinct exosomal miRNAs was altered after RIC intervention, potentially involving multiple pathways. Conclusion: Exosomes appear to play a pivotal role in the protective effects induced by RIC. Clarifying their function in RIC under different pathological situations represents a grand challenge for future research.

Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling antigen release, typically involving various approaches at the injection site. Yet, strategies for intracellular slow-release of antigens in vaccines are still unexplored. Our study showed that controlling the degradation of antigens in dendritic cells and slowing their transport from early endosomes to lysosomes markedly enhances both antigen-specific T-cell immune responses and germinal center B cell responses. This leads to the establishment of sustained humoral and cellular immunity in vivo imaging and flow cytometry indicated this method not only prolongs antigen retention at the injection site but also enhances antigen concentration in lymph nodes, surpassing traditional Aluminium (Alum) adjuvants. Additionally, we demonstrated that the slow antigen degradation induces stronger follicular helper T cell responses and increases proportions of long-lived plasma cells and memory B cells. Overall, these findings propose that controlling the speed of antigens transport in dendritic cells can significantly boost vaccine efficacy, offering an innovative avenue for developing highly immunogenic next-generation vaccines.

IntroductionPersistent infections caused by certain viruses and parasites have been associated with multiple diseases and substantial mortality. Heavy metals are ubiquitous environmental pollutants with immunosuppressive properties. This study aimed to determine whether heavy metals exposure suppress the immune system, thereby increasing the susceptibility to persistent infections.MethodsUsing data from NHANES 1999–2016, we explored the associations between heavy metals exposure and persistent infections: Cytomegalovirus (CMV), Epstein–Barr Virus (EBV), Hepatitis C Virus (HCV), Herpes Simplex Virus Type–1 (HSV–1), Toxoplasma gondii (T. gondii), and Toxocara canis and Toxocara cati (Toxocara spp.) by performing logistic regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Mediation analysis was used to determine the mediating role of host immune function in these associations.ResultsLogistic regression analysis revealed positive associations between multiple heavy metals and the increased risk of persistent infections. In WQS models, the heavy metals mixture was associated with increased risks of several persistent infections: CMV (OR: 1.58; 95% CI: 1.17, 2.14), HCV (OR: 2.94; 95% CI: 1.68, 5.16), HSV–1 (OR: 1.25; 95% CI: 1.11, 1.42), T. gondii (OR: 1.97; 95% CI: 1.41, 2.76), and Toxocara spp. (OR: 1.76; 95% CI: 1.16, 2.66). BKMR models further confirmed the combined effects of heavy metals mixture and also identified the individual effect of arsenic, cadmium, and lead. On mediation analysis, the systemic immune inflammation index, which reflects the host’s immune status, mediated 12.14% of the association of mixed heavy metals exposure with HSV–1 infection.DiscussionThe findings of this study revealed that heavy metals exposure may increase susceptibility to persistent infections, with the host’s immune status potentially mediating this relationship. Reducing exposure to heavy metals may have preventive implications for persistent infections, and further prospective studies are needed to confirm these findings.

Adopting drought-tolerant (DT) cultivars is an effective strategy to sustain maize (Zea mays L.) production under water shortage. Optimizing plant density is an important management practice for improving maize yield. In a two-year field trial, the response of yield, actual evapotranspiration (ETc act), and water productivity (WP) to plant density (6, 7.5, 9 plants m−2) was assessed under irrigated and rainfed conditions using a DT (ZD958) and a drought-susceptible (DS, ZY309) maize cultivar, and additionally, the comparison of soil water depletion will be conducted among soils growing different DT maize varieties. Under rainfed, average yield, ETc act, and WP were 24.7%, 8.6% and 14.8% greater in ZD958 than ZY309, respectively. When density increased from 6 to 9 plants m−2, for ZD958 and ZY309 ETc act remained relatively constant, whereas their yield and WP first increased and then decreased and ultimately reached their maximum at 7.5 plants m−2. Under irrigation, increasing density (6–9 plants m−2) significantly increased yield and WP for ZD958, but for ZY309, yield and WP were not significantly impacted. Yield across seasons did not differ between cultivars at 6 and 7.5 plants m−2, and ZD958 had a 10.2% yield advantage over ZY309 at 9 plants m−2. The findings imply that DT cultivar showed greater high density tolerance than DS cultivar and thus higher optimal density under irrigation. Under rainfed, both cultivars had similar density tolerance and optimum density, whereas DT cultivar had stronger drought tolerance than DS cultivar, which could explain DT cultivar’s greater yield and WP. This study indicate that DT cultivar showed higher and more stable yields than DS cultivar across rainfed and irrigated conditions when grown at optimal densities. Thus, sustainable maize production could be achieved by adopting DT cultivars and optimizing density for different conditions in the study region.

Abstract Background Cadmium (Cd) and lead (Pb) exhibit nephrotoxic activity and may accelerate kidney disease complications in diabetic patients, but studies investigating the relation to diabetic kidney disease (DKD) have been limited. We aimed to examine the associations of Cd and Pb with DKD in diabetic patients. Methods 3763 adults with blood metal measurements and 1604 adults with urinary ones who were diabetic from National Health and Nutrition Examination Survey (NHANES) 2007–2016 were involved. Multivariate logistic regression models were used to analyze the associations of blood Cd (BCd), blood Pb (BPb), urinary Cd (UCd), and urinary Pb (UPb) with DKD. Results BPb, BCd, and UCd levels were higher among participants with DKD than diabetics without nephropathy, but UPb performed the opposite result. BPb and UCd were significantly associated with DKD in the adjusted models (aOR, 1.17 (1.06, 1.29);1.52 (1.06, 2.02)). Participants in the 2nd and 3rd tertiles of BPb and BCd levels had higher odds of DKD, with a significant trend across tertiles, respectively (all P-trend

Based on a line-of-sight (LOS) guidance law for a curve parametrized path, a finite-time backstepping control is proposed for the kinematic path-following of an underactuated autonomous surface vehicle (ASV). Finite-time observer is utilized to estimate the unknown external disturbances accurately. The first-order Levant differentiator is introduced into the finite-time filter technique, such that the output of filter can not only approximate the derivative of the virtual control, but also avoid the singularity problem of real heading control. The integral terminal sliding mode is employed to improve the tracking performance and converging rate in the surging velocity control. By virtue of Lyapunov function, all the signals in the closed-loop system can be guaranteed uniformly ultimate boundedness, and accurate path-following task can be fulfilled in finite time. The simulation results and comparative analysis validate the effectiveness and robustness of the proposed control approach.