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Based on logging, core, thin section and geochemical analysis, the tectonic-lithofacies paleogeographic pattern of first member to third member of Ordovician Majiagou Formation (O1m1–O1m3 for short) in Ordos Basin is reconstructed, and the tectono-sedimentary evolution characteristics and oil-gas geological significance are discussed. The results are obtained in four aspects. First, a set of marginal argillaceous dolomites with high gamma ray value developed steadily and diachronously at the bottom of Majiagou Formation, which distributed over the Huaiyuan Movement unconformity, with δ13C values positive drift characteristics comparable to global transgression of the Early Ordovician Floplian. Second, the global sea level rose and the ancient land was submerged into the underwater uplift in O1m1 to O1m2, and the central uplift was deposited for the first time in the Ordovician, forming a tectonic pattern of “one uplift and two depressions”. Subsequently, the subduction and extrusion outside the basin and the differentiation of uplift and depression in the basin of O1m3 resulted in the activation of the Wushenqi–Jingbian bulge. Third, the evolution of the tectonic pattern had a significant impact on the sedimentary paleoenvironment. The O1m1 overlaps westward, and saline lagoon is formed in eastern depression and influenced by the transgression. The transgression continued in O1m2 and resulted in communication with the wide sea, and the large-scale grain shoal developed around eastern depression, and the late dry shrinkage formed a small scale evaporite lagoon in upper part. Under the influence of highland sealing in O1m3, the water body gradually differentiated into dolomitic gypsum and saline lagoons to the east, and the grain shoal spread along the highs around sag. Fourth, the source rocks developed diachronously at the bottom of Majiagou Formation form a favorable source-reservoir assemblage with the shoal facies reservoir distributed around the slope of O1m2–O1m3, and they have certain exploration potential for natural gas.

Abstract Aim To explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes. Methods Twenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables. Results In the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network. Conclusion Unlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients.

Abstract CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with “one to more” aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics.

Abstract The Camellia oleifera meal (COM), a primary byproduct of oil-tea processing, often being discarded or used as a low-grade fertilizer due to its low value. The underutilization has become a significant bottleneck hindering the high-quality development of the oil-tea industry. In this study, the production of antibiotic-free feed additives through the solid-state fermentation of COM by Acremonium terricola was investigated. Our findings revealed that a saponin concentration of 5 mg/mL significantly enhanced the production of cordycepic acid (70.4 mg/g), ergosterol (3.32 mg/g), and chitin (110 mg/g) by A. terricola. This concentration also promoted chitin production and the activities of peroxidase (POD) and Na+/K+-ATPase, thereby maintaining cellular homeostasis and energy balance in A. terricola. Solid-state fermented rice bran (RB), wheat bran (WB), and desaponificated COM (containing 2.6 mg/100 g of tea saponin) were all found to be beneficial for increasing the production of cordycepic acid and ergosterol. The blend of COM, RB, and WB in the ratio of 15:65:20 was particularly advantageous for the production and accumulation of cordycepic acid and ergosterol, yielding 1.54 and 1.43 times, 1.27 and 1.37 times, and 1.98 and 5.52 times more than those produced by WB, RB, and COM alone, respectively.Meantime, the difference in contents of sugar and protein in A. terricola cultures (ATCs) using combination were not significant compared to RB and WB. These results indicated that COM can partially replace foodstuffs or food by-products to prepare antibiotic-free feed additives by A. terricola. Graphical Abstract

Abstract Background This study aims to report the phenomenon of Myelin oligodendrocyte glycoprotein antibody-associated encephalitis induced by Mycoplasma pneumoniae infections and promote the potential benefits of combining early immunotherapy and anti-M—pneumoniae therapy for these patients. Methods Three children with MOG-IgG-associated encephalitis due to M. pneumoniae infections who were treated at our hospital from September to November 2023 were included in the study. We investigated and analyzed the background and clinical features of these patients. Results Three patients developed headaches, seizures, and/or other neurological manifestations, elevated mononuclear cells in cerebrospinal fluid, intracranial lesions on cranial magnetic resonance imaging (MRI), and positive MOG-IgG in serum, within 10–14 days. They were diagnosed with MOG-IgG-associated encephalitis due to M. pneumoniae infections, the treatment consisted of intravenous immunoglobulin, glucocorticoid, and erythromycin, then they were completely recovered. Conclusion Mycoplasma pneumoniae (M. pneumoniae) infections can cause oligodendrocyte glycoprotein (MOG) antibody-associated encephalitis. The recognition of this condition will promote the potential benefits of combining early immunotherapy and anti-M. pneumoniae therapy for patients with MOG-IgG-associated encephalitis.

Abstract Background The health as expanding consciousness (HEC) theory posits that health and disease are interconnected components of a comprehensive process aimed at expanding consciousness. Aim The objective of this study is to introduce the concept, research status and applications of HEC and offer a comprehensive understanding of its various key components. Data sources Databases including EMBASE, PubMed, ScienceDirect, ProQuest, Wiley, Web of Science, Sinomed, China National Knowledge Infrastructure, Wanfang, and CQVIP, covering the period from 1986 to 2023. Method Employing Rodgers’ evolutionary concept analysis approach, this study included and analysed 70 studies. Results The characteristics of HEC comprise aspects such as movement, time, space, energy, rhythm, and paradigm of health. The antecedents of HEC encompass disease, chaos, binding, centring, and choice point. Consequences associated with HEC include self-transcendence, unbinding, decentring, expanded consciousness, real freedom, pattern recognition, absolute consciousness, and death. Conclusion This study has identified substitute terms, related concepts, attributes, antecedents, consequences, and empirical references associated with HEC. The findings provide valuable information applicable across various domains of nursing, encompassing practice, education, research, and management.

Abstract Depression is a common psychiatric disorder among patients undergoing maintenance haemodialysis (MHD). Depression may reportedly contribute to poor prognosis in several ways, including its effects on platelet function. We hypothesised that depression contributes to the occurrence of cardiocerebral vascular events (CCVE) and dysfunction of arteriovenous fistula (DAVF) in patients undergoing MHD through its effects on platelets. In this prospective cohort study, patients undergoing MHD were recruited and divided into depression and non-depression groups according to their Hamilton Depression Scale (HAMD) scores. The 286 enrolled patients had 103 occurrences of depressive symptoms (prevalence = 36.01%). Compared with the non-depression group, depression group had a significantly higher cumulative prevalence of CCVE and DAVF during follow-up. Cox regression analysis indicated that higher HAMD scores and lower plasma platelet distribution width (PDW) were common risk factors for CCVE and DAVF. Furthermore, HAMD scores were significantly negatively correlated with plasma PDW and was the main variable affecting changes in PDW, as indicated by multiple linear regression analysis. Depression may increase the risk of CCVE and DAVF in patients undergoing MHD by activating platelets. Plasma PDW may be a convenient indicator of platelet activation status and may predict the risk of CCVE and DAVF.

Abstract Pyroelectric (PE) detection technologies have attracted extensive attention due to the cooling-free, bias-free, and broadband properties. However, the PE signals are generated by the continuous energy conversion processes from light, heat, to electricity, normally leading to very slow response speeds. Herein, we design and fabricate a PE detector which shows extremely fast response in near-infrared (NIR) band by combining with the inhomogeneous plasmonic metasurface. The plasmonic effect dramatically accelerates the light-heat conversion process, unprecedentedly improving the NIR response speed by 2−4 orders of magnitude to 22 μs, faster than any reported infrared (IR) PE detector. We also innovatively introduce the concept of time resolution into the field of PE detection, which represents the detector’s ability to distinguish multiple fast-moving targets. Furthermore, the spatially inhomogeneous design overcomes the traditional narrowband constraint of plasmonic systems and thus ensures a wideband response from visible to NIR. This study provides a promising approach to develop next-generation IR PE detectors with ultrafast and broadband responses.

Conventional thermosetting polymers, mostly derived from nonrenewable petroleum resources, are not reprocessable and recyclable due to their highly cross-linked three-dimensional networks and face the disadvantage of high flammability. To solve these issues, in this study, we synthesized a novel Schiff base covalent adaptable thermoset from a furan-derived tri-aldehyde monomer (TMFP) and a furan-derived di-amine monomer (DFDA). The as-prepared TMFP-DFDA-Vitrimer exhibited superior anti-flammability with a high limiting oxygen index (LOI) of 35.0% and a UL-94 V-0 rating, which was attributed to the excellent charring ability. Additionally, TMFP-DFDA-Vitrimer could also be conveniently recycled by chemical decomposition under a mixed hydrochloric acid/tetrahydrofuran (HCl/THF) solution. After recycling for 5 times, the thermal, mechanical, and flame retardant properties of the recycled TMFP-DFDA-Vitrimer retained almost unchanged compared to the original one. This work provides a prime instance to develop advanced thermosetting polymers from abundant furan-based compounds.

Abstract Background To investigate the safety and effectiveness of non-viscoelastic agent technique for EVO-ICL implantation. Methods A total of 181 myopia eyes that underwent non-toric ICL without viscoelastic agent through single incision from Beijing Tongren Hosipital were included. An analysis was conducted on the quantity of haptics that were initially implanted intraoperatively into the posterior chamber. Intraocular pressure (IOP) was evaluated at before and 2 h,24 h,1week,6month after surgery. Anterior chamber volume(ACV), anterior chamber depth(ACD), anterior chamber angle(ACA), pupil diameter(PD) and corneal densitometry density (ECD) were evaluated at before and 24 h postoperatively. Refractive outcomes were investigated at before, 24 h ,7 days and 6months. Vault was evaluated at 24 h ,7 days and 6months. Results The efficacy and safety indices were 1.30 ± 0.32 and 1.31 ± 0.32, respectively. Of 181 eyes, 99 eyes received 4 haptics on the first attempt without any adjustment, and 72 eyes received lens alignment without an viscoelastic agent. The success rate of the viscoelastic agent free procedure was 94.5%. Two hours postoperatively, IOP was 17.41 ± 3.77 mmHg, which was significantly higher than baseline value (t = 8.930, P

Abstract An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients.

Editorial “When something is said to be impossible, there are two points for researchers to initially clarify: whether it really is forbidden by the laws of nature; or whether it is simply that no material that currently exists in nature can do that.” Metamaterials are such magical beings, which have physical properties like invisibility, negative refraction, super-resolution, and perfect absorption that are absent from natural materials. It has been rated by Science as one of the top ten scientific and technological breakthroughs affecting human beings in the 21st century. In this issue of Light People, we spoke with a “magic” creator, Professor Che Ting Chan, the Associate Vice-President (Research & Development) of the Hong Kong University of Science and Technology (HKUST), Member of the Hong Kong Academy of Sciences and Fellow of the American Physical Society. He has researched a number of theoretical problems in material physics, investigated the theory behind what they seek to achieve, and modulated light (electromagnetism) and acoustic waves through metamaterials. In the following, let’s take a closer look at Professor Che Ting Chan’s research life, and appreciate his style and the background of his accomplishment.

Abstract Factor-dependent termination uses molecular motors to remodel transcription machineries, but the associated mechanisms, especially in eukaryotes, are poorly understood. Here we use single-molecule fluorescence assays to characterize in real time the composition and the catalytic states of Saccharomyces cerevisiae transcription termination complexes remodeled by Sen1 helicase. We confirm that Sen1 takes the RNA transcript as its substrate and translocates along it by hydrolyzing multiple ATPs to form an intermediate with a stalled RNA polymerase II (Pol II) transcription elongation complex (TEC). We show that this intermediate dissociates upon hydrolysis of a single ATP leading to dissociation of Sen1 and RNA, after which Sen1 remains bound to the RNA. We find that Pol II ends up in a variety of states: dissociating from the DNA substrate, which is facilitated by transcription bubble rewinding, being retained to the DNA substrate, or diffusing along the DNA substrate. Our results provide a complete quantitative framework for understanding the mechanism of Sen1-dependent transcription termination in eukaryotes.

Introduction: Etomidate is commonly used to induce anesthesia in cardiac surgery patients due to its favorable cardiovascular profile. Sedative-hypnotic effects are mediated by gammaaminobutyric acid (GABA) receptor complexes in the central nervous system. There are numerous studies in which etomidate and other drugs are compared in terms of their clinical outcomes. The relative efficacy and safety of etomidate, however, remains inconclusive. In this study, we performed a systematic analysis of randomized controlled trials to assess the impact of etomidate, on patients undergoing cardiac surgery, with respect to patient outcome and adverse events. Methods: A systematic review was conducted of all existing clinical trials exploring the safety and efficacy of etomidate in patients undergoing cardiac surgery. Randomized controlled trials (RCTs) that compared etomidate with other drugs during induction in adult cardiac surgery assessing hemodynamic parameters and clinical outcomes were included, while studies involving non-cardiac or pediatric surgery and those lacking relevant outcome data were excluded. Primary outcomes were all-cause 30-day mortality. Secondary outcomes included duration of tracheal intubation, duration of intensive care unit (ICU) stay, duration of hospital stay, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and other hemodynamic parameters, vasopressor requirements after induction and intubation, cortisol levels, and incidence of myoclonus. Results: Sixteen randomized controlled trials involving 1162 patients were included. Etomidate did not affect the all-cause 30-day mortality of patients undergoing cardiac surgery compared to comparator drugs (RR, 0.96; 95 % CI, 0.26 to 3.49; P = 0.95). There were no significant differences in the duration of tracheal intubation (MD, −0.08 h; 95 % CI, −1.96 to 1.81; P = 0.94), the duration of ICU stay (MD, −2.07 h; 95 % CI, −8.09 to 3.96; P = 0.50) or the duration of hospital stay (MD, −0.62 d; 95 % CI, −2.25 to 1.00; P = 0.45) when etomidate was compared to comparator drugs. Patients receiving etomidate demonstrated a more stable hemodynamic profile after induction and intubation compared to those receiving comparator drugs. The requirement of a vasopressor after induction and intubation was significantly reduced with etomidate compared with those with comparator drugs (RR, 0.37; 95 % CI, 0.25 to 0.56; P

IntroductionMental health problems, especially depressive symptoms, are becoming increasingly prominent, posing a significant risk to public health. Changes in the body mass index (BMI) may impact an individual’s mental health, however, the relationship between BMI and depressive symptoms is unclear. The purpose of this study was to investigate the association between BMI and depressive symptoms.MethodsUsing a multi-stage sampling method, 10,686 adults in Longgang District, Shenzhen City, Guangdong Province, China, were selected for participation in this study. Surveys were distributed in 2020 and 2021 to measure participant demographic data and health. Binary logistic regression, restricted cubic spline regression, and subgroup analyses were performed to explore the relationship between BMI and depressive symptoms.ResultsThe results showed a U-shaped relationship between BMI and depression. Both obesity and underweight increased the risk of depression among the participants, especially in subgroups of participants who were young, highly educated, single and employed.ConclusionThese findings suggest that adults should try to maintain a normal body weight as a way to prevent depression and maintain their physical and mental health.

Despite the transformative impact of anti-PD-1/PD-L1 therapies, challenges such as low response rates persist. The stimulator of interferon genes (STING) pathway, a crucial element of innate immunity, emerges as a strategic target to overcome these limitations. Understanding its multifaceted functions in cancer, including antigen presentation and response to DNA damage, provides valuable insights. STING agonists, categorized into cyclic dinucleotides (CDNs) and non-CDNs, exhibit promising safety and efficacy profiles. Innovative delivery systems, including antibody-drug conjugates, nanocarriers, and exosome-based therapies, address challenges associated with systemic administration and enhance targeted tumor delivery. Personalized vaccines, such as DT-Exo-STING, showcase the adaptability of STING agonists for individualized treatment. These advancements not only offer new prospects for combination therapies but also pave the way for overcoming resistance mechanisms. This review focuses on the potential of targeting STING pathway to enhance cancer immunotherapy. The integration of STING agonists into cancer immunotherapy holds promise for more effective, personalized, and successful approaches against malignancies, presenting a beacon of hope for the future of cancer treatment.

Aims: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated. Methods and Results: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of Clostridium sporogenes (C.sp) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal C.sp and increased SFA are further validated. At last, by supplementing C.sp to ISO‐induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels. Conclusions: Clostridium abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota–SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF.

Key Clinical Message With no family history, and an atypical phenotype, the clinical diagnosing of Noonan syndrome (NS) can be very difficult. The present case emphasized that generalized edema in neonates may be the potential first symptom of NS. Abstract Severe generalized edema is a rare pathological condition with high mortality in newborns, in particular the premature infants. It is characterized by the extensive subcutaneous tissue edema and the accumulation of fluid in neonatal body fluid compartments. The etiology and pathogenesis of hydrops in neonates are quite complex. Generally speaking, hydrops can be divided into immune hydrops and non‐immune hydrops according to the etiology. It is still challenging in treating severe neonatal edema. In this study, we presented a preterm newborn with severe generalized edema after birth, which was finally diagnosed with Noonan syndrome (NS). The infant clinically manifested as severe generalized edema alone, without the involvement of multiple organ malformation. Generalized edema in neonates was probably the first symptom of NS. Therefore, differential diagnosis of NS is necessary for infants developing generalized edema.

Purpose: To investigate the change in the vault of the implantable collamer lens (ICL) under dark-to-light conditions and its association with anterior chamber and lens parameters in patients undergoing ICL surgery. Methods: In 76 eyes from 40 patients, preoperative anterior chamber volume (ACV), pupil diameter (PD), anterior chamber angle, central corneal thickness (CCT), white-to-white (WTW), lens thickness (LT), axial length (AL), spherical equivalent (SE) and patient's age were collected. Postoperative vault, PD and LT were measured under dark and light conditions using anterior segment optical coherence tomography (CASIA2; TOMEY, Japan), and changes and lens displacement under dark-to-light conditions were calculated. Mixed-effects models were used to analyze the correlation between the vault change and the anterior chamber and lens parameters of all subjects and the high-vault subgroup. Results: The vault under light condition (648.36 ± 304.47 μm) was significantly smaller compared to the vault under dark condition (708.89 ± 316.15 μm). In all patients, vault change increased with the increase of age, lens displacement and PD change; and increased with the decrease of ACV, LT change and baseline vault (under dark condition). In the high-vault subgroup, vault change increased with the increase of CCT, lens displacement and PD change; and increased with the decrease of ACV. Conclusions: ICL vault changes significantly from dark to light, influenced by age, ACV, PD change, LT change, lens displacement, and baseline vault. A higher baseline vault is correlated with a larger LT change, affecting the levels of accommodation under dark-to-light transition.

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a severe public health problem in Jiangxi province, China. Previous studies reported genetic variants of Orthohantavirus hantanense (Hantaan virus, HTNV) in rodents in this area. However, the relationship between HTNV variants and human infection needs to be confirmed. This study aimed to identify the HTNV variants in patients and to understand the clinical characteristics of HFRS caused by these variants.MethodsSamples were collected from hospitalized suspected cases of HFRS during the acute phase. HFRS cases were confirmed using quantitative real-time RT-PCR. Peripheral blood mononuclear cells (PBMC) from patients with HFRS were inoculated into Vero-E6 cells for viral isolation. The genomic sequences of HTNV from patients were obtained by amplicon-based next-generation sequencing. A retrospective analysis was conducted on the clinical characteristics of the patients.ResultsHTNV RNA was detected in 53 of 183 suspected HFRS patients. Thirteen HTNVs were isolated from 32 PBMCs of HFRS cases. Whole genome sequences of 14 HTNVs were obtained, including 13 isolates in cell culture from 13 patients, and one from plasma of the fatal case which was not isolated successfully in cell culture. Genetic analysis revealed that the HTNV sequence from the 14 patients showed significant variations in nucleotide and amino acid to the HTNV strains found in other areas. Fever (100%, 53/53), thrombocytopenia (100%, 53/53), increased serum aspartate aminotransferase (100%, 53/53), and increased lactate dehydrogenase (96.2%, 51/53) were the most common characteristics. Severe acute kidney injury was observed in 13.2% (7/53) of cases. Clinical symptoms, such as pain, petechiae, and gastrointestinal or respiratory symptoms were uncommon.ConclusionThe HTNV genetic variants cause human infections in Jiangxi. The clinical symptoms of HFRS caused by the HTNV genetic variant during the acute phase are atypical. In addition to renal dysfunction, attention should be paid to the common liver injuries caused by these genetic variants.

Summary: Background: Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC). Methods: We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models. Findings: The CID exhibited significant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) among patients with RCC tumors measuring 3 cm or larger (all p

Abstract Background Studies have revealed the effects of childhood adversity, anxiety, and negative coping on sleep quality in older adults, but few studies have focused on the association between childhood adversity and sleep quality in rural older adults and the potential mechanisms of this influence. In this study, we aim to evaluate sleep quality in rural older adults, analyze the impact of adverse early experiences on their sleep quality, and explore whether anxiety and negative coping mediate this relationship. Methods Data were derived from a large cross-sectional study conducted in Deyang City, China, which recruited 6,318 people aged 65 years and older. After excluding non-agricultural household registration and lack of key information, a total of 3,873 rural older adults were included in the analysis. Structural equation modelling (SEM) was used to analyze the relationship between childhood adversity and sleep quality, and the mediating role of anxiety and negative coping. Results Approximately 48.15% of rural older adults had poor sleep quality, and older adults who were women, less educated, widowed, or living alone or had chronic illnesses had poorer sleep quality. Through structural equation model fitting, the total effect value of childhood adversity on sleep quality was 0.208 (95% CI: 0.146, 0.270), with a direct effect value of 0.066 (95% CI: 0.006, 0.130), accounting for 31.73% of the total effect; the total indirect effect value was 0.142 (95% CI: 0.119, 0.170), accounting for 68.27% of the total effect. The mediating effects of childhood adversity on sleep quality through anxiety and negative coping were significant, with effect values of 0.096 (95% CI: 0.078, 0.119) and 0.024 (95% CI: 0.014, 0.037), respectively. The chain mediating effect of anxiety and negative coping between childhood adversity and sleep quality was also significant, with an effect value of 0.022 (95% CI: 0.017, 0.028). Conclusions Anxiety and negative coping were important mediating factors for rural older adult’s childhood adversity and sleep quality. This suggests that managing anxiety and negative coping in older adults may mitigate the negative effects of childhood adversity on sleep quality.

Abstract Biallelic mutations in the coenzyme Q7 (COQ7) encoding gene were recently identified as a genetic cause of distal hereditary motor neuropathy. Here, we explored the clinical, electrophysiological, pathological, and genetic characteristics of a Chinese patient with spastic paraplegia associated with recessive variants in COQ7. This patient carried a novel c.322C>A (p.Pro108Thr) homozygous variant. Sural biopsy revealed mild mixed axonal and demyelinating degeneration. Immunoblotting showed a significant decrease in the COQ7 protein level in the patient's fibroblasts. This study confirmed that COQ7 variant as a genetic cause of HSP, and further extended spastic paraplegia to the phenotypic spectrum of COQ7‐related disorders.

Abstract Introduction This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. Methods A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. Results On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0

Abstract Outdoor air pollution, particularly volatile organic compounds (VOCs), significantly contributes to the global health burden. Previous analyses of VOC exposure have typically focused on regional and national scales, thereby limiting global health burden assessments. In this study, we utilized a global chemistry-climate model to simulate VOC distributions and estimate related cancer risks from 2000 to 2019. Our findings indicated a 10.2% rise in global VOC emissions during this period, with substantial increases in Sub-Saharan Africa, the Rest of Asia, and China, but decreases in the U.S. and Europe due to reductions in the transportation and residential sectors. Carcinogenic VOCs such as benzene, formaldehyde, and acetaldehyde contributed to a lifetime cancer burden affecting 0.60 [95% confidence interval (95CI): 0.40–0.81] to 0.85 [95CI: 0.56–1.14] million individuals globally. We projected that between 36.4% and 39.7% of the global population was exposed to harmful VOC levels, with the highest exposure rates found in China (82.8–84.3%) and considerably lower exposure in Europe (1.7–5.8%). Open agricultural burning in less-developed regions amplified VOC-induced cancer burdens. Significant disparities in cancer burdens between high-income and low-to-middle-income countries were identified throughout the study period, primarily due to unequal population growth and VOC emissions. These findings underscore health disparities among different income nations and emphasize the persistent need to address the environmental injustice related to air pollution exposure.

ABSTRACTMyotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

Abstract Here, a separation‐free and label‐free portable aptasensor is developed for rapid and sensitive analysis of tumor‐derived exosomes (TEXs). It integrated a parallel rolling circle amplification (RCA) reaction, selective binding of metal ions or small molecules to nucleic acid‐specific conformations, and a low‐cost, highly sensitive handheld fluorometer. Lung cancer, for example, is targeted with two typical biomarkers (mucin 1 and programmed cell death ligand 1 (PD‐L1)) on its exosomes. The affinity of aptamers to the targets modulated the amount of RCA products (T‐Hg2+‐T and cytosine (C)‐rich single‐stranded DNA), which in turn affected the fluorescence intensity of quantum dots (QDs) and methylene blue (MB). The results revealed that the limit of detection (LOD) of the handheld fluorometer for cell‐derived exosomes can be as low as 30 particles mL−1. Moreover, its specificity, sensitivity, and area under the curve (AUC) are 93% (14/15), 92% (23/25), and 0.956, as determined by the analysis of 40 clinical samples. Retesting 16 of these samples with the handheld fluorometer yielded strong concordance between the fluorometer results and those acquired from clinical computed tomography (CT) and pathology.

BackgroundVascular dementia (VaD) is one of the most prevalent, burdensome, and costly forms of dementia. Pharmacological treatment is often the first-line choice for clinicians; however, there is a paucity of comparative information regarding the multiple available drug options.Methods and AnalysisA systematic review and network meta-analysis were conducted on randomized trials involving adult patients with VaD, sourced from PubMed, the Cochrane Library, EMBASE, Web of Science, OPENGREY, ClinicalTrials.gov, Wanfang Data, and CNKI. The primary outcomes included changes in Mini-Mental State Examination (MMSE) scores, activities of daily living (ADL) scores, and the incidence of adverse reactions. Efficacy and safety of intervention strategies were comprehensively analyzed using forest plots, cumulative ranking probability curves (SUCRA), and funnel plots, all generated with R software.ResultsA total of 194 RCTs comparing 21 different anti-VaD drugs with placebos or no treatment were analysed. Regarding MMSE scores, the five most effective drugs were Butylphthalide, Huperzine A, Edaravone, Rivastigmine, and Memantine. For ADL scores, the top five drugs in efficacy were Huperzine A, Butylphthalide, Tianzhi granule, Nicergoline, and Idebenone. In terms of the incidence of adverse drug reactions, Co-dergocrine Mesylate, Tongxinluo capsule, Butylphthalide, Piracetam, and Oxiracetam demonstrated favourable safety profiles.ConclusionThis study enhances the understanding of the relative benefits and risks associated with various VaD treatments, providing a valuable reference for clinical decision-making.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier registration number.

ObjectivesTo evaluate the effectiveness and safety of Chinese herbal footbaths (CHF) as an adjunctive therapy in managing dysmenorrhea.MethodsTen electronic databases were searched to identify eligible randomized clinical trials (RCTs) from inception until June 2023. Outcome measurements encompassed the total effective rate, visual analog scale (VAS) score of pain intensity, Cox menstrual symptom scale (CMSS) score, symptom score, Traditional Chinese Medicine (TCM) syndrome scale, and any reported adverse events. The methodological quality of the included studies was assessed with the Cochrane collaboration tool. Review Manager 5.3 software was employed for quantitative synthesis, and funnel plots were utilized to evaluate potential reporting bias.ResultsEighteen RCTs with 1,484 dysmenorrhea patients were included. The aggregated results suggested that the adjunctive CHF could significantly ameliorate dysmenorrhea, as evident from the improved total effective rate [risk ratio (RR) 1.18, 95% confidence interval (CI): 1.12 to 1.23, P < 0.00001], VAS (MD 0.88, 95% CI: 0.68 to 1.09, P < 0.00001), CMSS (MD 3.61, 95% CI: 2.73 to 4.49, P < 0.00001), symptom score (SMD 1.09, 95% CI: 0.64 to 1.53, P < 0.00001), and TCM syndrome scale (MD 3.76, 95% CI: 2.53 to 4.99, P < 0.0001). In addition, CHF presented fewer adverse events with a better long-term effect (RR 1.34, 95% CI: 1.11 to 1.63, P < 0.01) and diminished recurrence rate (RR 0.19, 95% CI: 0.09 to 0.39, P < 0.0001).ConclusionCurrent evidence implies that CHF may be an effective and safe adjunctive therapy for patients with dysmenorrhea. However, the methodological quality of the studies included was undesirable, necessitating further verification with more well-designed and high-quality multicenter RCTs.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=188256, identifier registration number.

The tumor microenvironment is increasingly acknowledged as a critical contributor to cancer progression, mediating genetic and epigenetic alterations. Beyond diverse cellular interactions from the microenvironment, physicochemical factors such as tumor acidosis also significantly affect cancer dynamics. Recent research has highlighted that tumor acidosis facilitates invasion, immune escape, metastasis, and resistance to therapies. Thus, noninvasive measurement of tumor acidity and the development of targeted interventions represent promising strategies in oncology. Techniques like contrast-enhanced ultrasound (CEUS) can effectively assess blood perfusion, while ultrasound-stimulated microbubble cavitation (USMC) has proven to enhance tumor blood perfusion. We therefore aimed to determine whether CEUS assesses tumor acidity and whether USMC treatment can modulate tumor acidity. Firstly, we tracked CEUS perfusion parameters in MCF7 tumor models and compared them with in vivo tumor pH recorded by pH microsensors. We found that the peak intensity and area under curve of tumor contrast-enhanced ultrasound correlated well with tumor pH. We further conducted USMC treatment on MCF7 tumor-bearing mice, tracked changes of tumor blood perfusion and tumor pH in different perfusion regions before and after the USMC treatment to assess its impact on tumor acidity and optimize therapeutic ultrasound pressure. We discovered that USMC with 1.0 Mpa significantly improved tumor blood perfusion and tumor pH. Furthermore, tumor vascular pathology and PGI2 assays indicated that improved tumor perfusion was mainly due to vasodilation rather than angiogenesis. More importantly, analysis of glycolysis-related metabolites and enzymes demonstrated USMC treatment can reduce tumor acidity by reducing tumor glycolysis. These findings support that CEUS may serve as a potential biomarker to assess tumor acidity and USMC is a promising therapeutic modality for reducing tumor acidosis.

Summary: Current studies in early cancer detection based on liquid biopsy data often rely on off-the-shelf models and face challenges with heterogeneous data, as well as manually designed data preprocessing pipelines with different parameter settings. To address those challenges, we present AutoCancer, an automated, multimodal, and interpretable transformer-based framework. This framework integrates feature selection, neural architecture search, and hyperparameter optimization into a unified optimization problem with Bayesian optimization. Comprehensive experiments demonstrate that AutoCancer achieves accurate performance in specific cancer types and pan-cancer analysis, outperforming existing methods across three cohorts. We further demonstrated the interpretability of AutoCancer by identifying key gene mutations associated with non-small cell lung cancer to pinpoint crucial factors at different stages and subtypes. The robustness of AutoCancer, coupled with its strong interpretability, underscores its potential for clinical applications in early cancer detection.

IntroductionIn hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling through the serum and glucocorticoid inducible kinase-1 (SGK-1) can impact cytokine abundance. Here, we hypothesize that SGK-1 impacts production of additional aortic pathologic markers (APMs) representing VSMC dysfunction in HTN.MethodsAortic VSMC expression of APMs was quantified by QPCR in cyclic biaxial stretch (Stretch) +/− AngiotensinII (AngII). APMs were selected to represent VSMC dedifferentiated transcriptional activity, specifically Interleukin-6 (IL-6), Cathepsin S (CtsS), Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). To further assess the effect of tension alone, abdominal aortic rings from C57Bl/6 WT mice were held in a myograph at experimentally derived optimal tension (OT) or OT + 30% +/−AngII. Dependence on SGK-1 was assessed by treating with EMD638683 (SGK-1 inhibitor) and APMs were measured by QPCR. Then, WT and smooth muscle cell specific SGK-1 heterozygous knockout (SMC-SGK-1KO+/−) mice had AngII-induced HTN. Systolic blood pressure and mechanical stress parameters were assessed on Day 0 and Day 21. Plasma was analyzed by ELISA to quantify APMs. Statistical analysis was performed by ANOVA.ResultsIn cultured aortic VSMCs, expression of all APMs was increased in response to biomechanical stimuli (Stretch +/−AngII,). Integrating the matrix contribution to signal transduction in the aortic rings led to IL-6 and CysC demonstrating SGK-1 dependence in response to elevated tension and interactive effect with concurrent AngII stimulation. CtsS and TNC, on the other hand, primarily responded to AngII, and OPG expression was unaffected in aortic ring experimentation. Both mouse strains had >30% increase in blood pressure with AngII infusion, reduced aortic distensibility and increased PPV, indicating increased aortic stiffness. In WT + AngII mice, IL-6, CtsS, CysC, and TNC plasma levels were significantly elevated, but these APMs were unaffected by HTN in the SMC-SGK-1KO+/− +AngII mice, suggesting SGK-1 plays a major role in VSMC biomechanical signaling to promote dysfunctional production of selected APMs.ConclusionIn HTN, changes in the plasma levels of markers associated with aortic matrix homeostasis can reflect remodeling driven by mechanobiologic signaling in dysfunctional VSMCs, potentially through the activity of SGK-1. Further defining these pathways may identify therapeutic targets to reduce cardiovascular morbidity and mortality.

The solutions for the electrostatic interacting force between a particle and a plane typically assume that the plane is infinite and the particle can be approximated as a point charge. Nevertheless, the prerequisites of underlying assumptions of these calculations remain unspecified, resulting in the inability to assess the reliability of the results and constraining the practical applicability of analytical models. In this paper, the authors introduce the particle–coated plane electrostatic interaction model by employing the re-expansion method. Additionally, the multipole–coated plane electrostatic interaction model is presented using the image multipole method. An analysis of the assumptions’ prerequisites is conducted, considering a relative error of less than 2 % as the approximate standard. The findings indicate that, irrespective of the material properties of the particle and plane, the radius of the planar plate must exceed three times the distance between the particle’s center and the plane to satisfy the infinite plane assumption. When the distance between the particle’s center and the plane surpasses three times the radius, it is permissible to approximate the charged particle as a point charge. The study presented in this paper establishes a standard for prior estimation of the departure range in existing analytical models related to particle–plane electrostatic interaction. This work also serves as a theoretical basis for the practical application of these models in engineering.

Abstract Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Abstract Background Peutz-Jeghers syndrome (PJS), an autosomal dominant multiple cancerous disorder, is clinically characterized by mucocutaneous macules and multiple gastrointestinal hamartomatous polyps. Gastric-type endocervical adenocarcinoma (G-EAC), a special subtype of cervical adenocarcinoma with non-specific symptoms and signs, is known to occur in approximately 11% of female patients with PJS. Case presentation Here, we report a case of PJS in a 24-year-old female with multiple mucocutaneous black macules who complained of vaginal discharge and menorrhagia. Moreover, we first described the multimodal ultrasonographical manifestations of PJS-correlated G-EAC. The three-dimensional reconstructed view of G-EAC on 3D realisticVue exhibited a distinctive “cosmos pattern” resembling features on magnetic resonance imaging, and the contrast-enhanced ultrasound displayed a “quick-up and slow-down” pattern of the solid components inside the mixed cervical echoes. We reported the multimodal ultrasonographical characteristics of a case of PJS-related G-EAC, as well as reviewed PJS-related literature and medical imaging features and clinical characteristics of G-EAC to provide insight into the feasibility and potential of utilizing multimodal ultrasonography for the diagnosis of G-EAC. Conclusions Multimodal ultrasound can visualize morphological features, solid components inside, and blood supplies of the G-EAC lesion and distinguish the G-EAC lesion from normal adjacent tissues. This facilitates preoperative diagnosis and staging of PJS-related G-EAC, thereby aiding subsequent health and reproductive management for patients with PJS.

Abstract Objective To explore the feasibility of the golden-angle radial sparse parallel (GRASP) dynamic magnetic resonance imaging (MRI) technique in predicting the intraoperative bleeding risk of scar pregnancy. Methods A total of 49 patients with cesarean scar pregnancy (CSP) who underwent curettage and GRASP-MRI imaging were retrospectively selected between January 2021 and July 2022. The pharmacokinetic parameters, including Wash-in, Wash-out, time to peck (TTP), initial area under the curve (iAUC), the transfer rate constant (Ktrans), constant flow rate (Kep), and volume of extracellular space (Ve), were calculated. The amount of intraoperative bleeding was recorded by a gynecologist who performed surgery, after which patients were divided into non-hemorrhage (blood loss ≤ 200 mL) and hemorrhage (blood loss > 200 mL) groups. The measured pharmacokinetic parameters were statistically compared using the t-test or Mann–Whitney U test with a significant level set to be p 200 mL) during curettage. The hemorrhage group had larger Wash-in, iAUC, Ktrans, Ve, and shorter TTP than the non-hemorrhage group (all P > 0.05). Wash-in had the highest AUC value (0.90), while Ktrans had the lowest value (0.67). Wash-out and Kep were not significantly different between the two groups. Conclusion GRASP DCE-MRI has the potential to forecast intraoperative hemorrhage during curettage treatment of CSP, with Wash-in exhibiting the highest predictive performance. This data holds promise for advancing personalized treatment. However, further study is required to compare its effectiveness with other risk factors identified through anatomical MRI and ultrasound.

Wideband spectrum sensing with a high-speed analog-digital converter (ADC) presents a challenge for practical systems. The Nyquist folding receiver (NYFR) is a promising scheme for achieving cost-effective real-time spectrum sensing, which is subject to the complexity of processing the modulated outputs. In this case, a multipath NYFR architecture with a step-sampling rate for the different paths is proposed. The different numbers of digital channels for each path are designed based on the Chinese remainder theorem (CRT). Then, the detectable frequency range is divided into multiple frequency grids, and the Nyquist zone (NZ) of the input can be obtained by sensing these grids. Thus, high-precision parameter estimation is performed by utilizing the NYFR characteristics. Compared with the existing methods, the scheme proposed in this paper overcomes the challenge of NZ estimation, information damage, many computations, low accuracy, and high false alarm probability. Comparative simulation experiments verify the effectiveness of the proposed architecture in this paper.

Abstract Background Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI. Methods Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd’s ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance. Results A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I 2 = 66.77%, p

Abstract Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment.

Abstract Background Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. Patients and methods PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. Results Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. Conclusion PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

Abstract Background Supraventricular tachycardia (SVT) is one of the most common non-benign arrhythmias in neonates, potentially leading to cardiac decompensation. This study investigated the early risk factors of acute heart failure (AHF) secondary to SVT in neonates, and explored their value in guiding the selection of effective anti-arrhythmic treatment. Methods A total of 43 newborns diagnosed with and treated for SVT between January 2017 and December 2022 were analyzed. According to the presence of AHF after restoring sinus rhythm in newborns with SVT, they were divided into SVT with AHF group and SVT without AHF group. Clinical data and anti-arrhythmic therapies were analyzed. Risk factors of AHF secondary to SVT in neonates were determined using logistic regression. The cut-off value for predictors of AHF secondary to SVT and demanding of a second-line anti-arrhythmic treatment was determined through receiver operating characteristic (ROC) analysis. Results Time to initial control of tachycardia > 24 h, hyperkalemia, anemia, and plasma B-type natriuretic peptide (BNP) were identified as risk factors of AHF secondary to SVT in neonates. BNP exhibited AUC of 0.80 in predicting AHF, and BNP > 2460.5pg/ml (OR 2.28, 95% CI 1.27 ~ 45.39, P = 0.03) was an independent predictor, yielding sensitivity of 70.6% and specificity of 84.6%. Neonates with BNP > 2460.5pg/ml (37.5% versus 7.4%, P = 0.04) had a higher demand for a second line anti-arrhythmic treatment to terminate SVT, with sensitivity and specificity for BNP in predicting at 75.0%, 71.4%, respectively. Conclusions BNP could be used to predict an incident of AHF secondary to SVT and a demand of second-line anti-arrhythmic treatment to promptly terminate SVT and prevent decompensation in neonates.

Abstract Re‐extracting environmentally transportable hexavalent uranium from wastewater produced by spent fuel reprocessing using the photocatalytic technology is a crucial strategy to avoid uranium pollution and recover nuclear fuel strategic resources. Here, we have designed S‐scheme 2D/0D C3N5/Fe2O3 heterojunction photocatalysts based on the built‐in electric field and the energy band bending theory, and have further revealed the immobilization process of hexavalent uranium conversion into relatively insoluble tetravalent uranium in terms of thermodynamics and kinetics. According to the results, the hexavalent uranium removal and recovery ratios in wastewater are as high as 93.38% and 83.58%, respectively. Besides, C3N5/Fe2O3 heterojunctions also exhibit satisfactory catalytic activity and selectivity even in the presence of excessive impurity cations (including Na+, K+, Ca2+, Mg2+, Sr2+, and Eu3+) or various organics (such as xylene, tributylphosphate, pyridine, tannic acid, citric acid, and oxalic acid). It is believed that this work can provide a potential opportunity for S‐scheme heterojunction photocatalysts to re‐enrich uranium from spent fuel wastewater.

Objectives: Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions.Methods: Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals.Results: A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly Guipiwan, Ease Pill, and Chaihu Jia Longgu Muli Decoction; the top three treatments on the reduction of HAMD scores were Chai Hu Shu Gan San, Xingnao Jieyu Decoction, and Xiaoyao Powder; and the top three treatments with the lowest adverse effects rates were Xiaoyao Powder, Alprazolam, and Xingnao Jieyu Decoction. Interestingly, commonly used synthetic drugs such as Fluoxetine, Escitalopram, Amitriptyline, Sertraline, Flupentixol and Melitracen, and Venlafaxine, not only appeared to be less effective than specific Chinese herbal medicines (Gan Mai Da Zao Decoction, Chaihu Jia Longgu Muli Decoction, Chai Hu Shu Gan San, Danzhi-Xiaoyao-San, and Xingnao Jieyu Decoction), but they were also related to substantially higher risk of adverse events.Conclusion: Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.

ObjectiveIn this study, we investigated the characteristics of the intestinal microbiota of preterm infants, and then analyzed the effects of probiotics supplementation on intestinal microbiota in preterm infants.MethodsThis study enrolled 64 infants born between 26 and 32 weeks gestational age (GA) and 22 full-term infants. 34 premature infants received oral probiotic supplementation for 28 days. Stool samples were obtained on the first day (D1) and the 28th day (D28) after birth for each infant. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System, specifically targeting the V3-V4 hyper-variable regions of the 16S rDNA gene. The sequencing results were then used to compare and analyze the composition and diversity index of the intestinal microbiota.ResultsThere was no significant difference in meconium bacterial colonization rate between premature and full-term infants after birth (p > 0.05). At D1, the relative abundance of Bifidobacterium, Bacteroides, and Lactobacillus in the stool of preterm infants was lower than that of full-term infants, and the relative abundance of Acinetobacter was higher than that of full-term infants. The Shannon index and Chao1 index of intestinal microbiota in preterm infants are lower than those in full-term infants (p < 0.05). Supplementation of probiotics can increase the relative abundance of Enterococcus and Enterobacter, and reduce the relative abundance of Escherichia and Clostridium in premature infants. The Chao1 index of intestinal microbiota decreased in preterm infants after probiotic supplementation (p < 0.05).ConclusionThe characteristics of intestinal microbiota in preterm infants differ from those in full-term infants. Probiotic supplementation can reduce the relative abundance of potential pathogenic bacteria and increase the abundance of beneficial microbiota in premature infants.

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

The medicine field continues to encounter obstacles in understanding the etiology of skin inflammation and the process of skin wound repair. Developing sustainable and effective three-dimensional (3D) skin models for investigating inflammatory skin biology remains a challenge. By incorporating halloysite nanotubes (HNT) into a composite collagen/alginate/hyaluronic acid hydrogel, we created a novel 3D skin model and introduced keratinocytes and fibroblast cells into it. We demonstrate that the modified 3D skin model is capable of enhancing the differentiation and adhesion behaviors of keratinocytes and fibroblast cells in vitro and promoting wound healing in vivo. These characteristics highlight the potential of this approach for the study of skin inflammation, wound healing, regeneration, aging, and beyond.

Abstract Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.