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Two new Cordyceps-like species, Perennicordyceps zongqii and Purpureocillium zongqii, isolated from a larva and soil, are introduced. Morphological comparisons and phylogenetic analyses based on multigene datasets (ITS, LSU, RPB2 and TEF) support the establishment of the new species. Moreover, new species in the families Polycephalomycetaceae and Ophiocordycipitaceae were introduced into Tiankeng and the valley for the first time. Further attention needs to be paid to the diversity of other Cordyceps-like fungi in the special eco-environment of the karst region.

Abstract This study explored the mechanism by which the m6A demethylase ALKBH5 mediates epithelial–mesenchymal transition (EMT) in sepsis‐associated acute kidney injury (SA‐AKI) and AKI‐chronic kidney disease (CKD) transition. HK‐2 cells were stimulated with lipopolysaccharide (LPS) to establish an in vitro model of SA‐AKI. ALKBH5 expression was reduced through the transfection of si‐ALKBH5. Cell viability, apoptosis, and migration were detected by CCK‐8 assay, TUNEL staining, and Transwell. The levels of TNF‐α, IL‐1β, and IL‐6 were measured by enzyme‐linked immunosorbent assay. Quantitative real‐time polymerase chain reaction or Western blotting was performed to determine the expressions of ALKBH5, miR‐205‐5p, DDX5, E‐cadherin, and α‐SMA. The m6A level was quantitatively analyzed. The expression of pri‐miR‐205 bound to DGCR8 and m6A‐modified pri‐miR‐205 after intervention with ALKBH5 expression was detected by RNA immunoprecipitation. A dual‐luciferase assay confirmed the binding between miR‐205‐5p and DDX5. ALKBH5 was highly expressed in LPS‐induced HK‐2 cells. Inhibition of ALKBH5 increased cell viability, repressed apoptosis, and reduced EMT. Inhibition of ALKBH5 increased the m6A modification level, thereby promoting DGCR8 binding to pri‐miR‐205 to increase miR‐205‐5p expression and eventually targeting DDX5 expression. Low expression of miR‐205‐5p or overexpression of DDX5 partially abolished the inhibitory effect of ALKBH5 silencing on EMT. In conclusion, ALKBH5 represses miR‐205‐5p expression by removing m6A modification to upregulate DDX5 expression, thereby promoting EMT and AKI‐CKD transition after SA‐AKI.

Previous studies of water use for coal-fired power generation may have overlooked inter-sectoral impacts in the supply chain. Indeed, to devise effective water conservation strategies during the ongoing energy transition, it is of utmost importance to analyze the sectoral water use structures and flows in the supply chain and identify the sources of water scarcity. Therefore, based on the power sector-split environmentally extended input‒output (EEIO) model and the life cycle assessment (LCA) idea, we comprehensively analyze the nexus between coal-fired power generation and water use from a sectoral perspective. Our findings reveal a complex and diverse water use structure in coal-fired power generation. The technology of production inherently determines the high intensity of water withdrawal, and the close intersectoral linkages, particularly with agriculture, construction, and some industrial sectors, in the production process result in an intricate web of indirect water withdrawal and blue water footprint (WF). Moreover, the grey WF, primarily sourced from coal mining and indirectly tied to tertiary industries, underscores critical areas for attention in water pollution management. Finally, water use in the coal-fired power sector is projected to remain at elevated levels in the short to medium term under various transition strategies. Following an in-depth exploration of the coal-fired power‒water use nexus, the findings can offer new perspectives and specific entry points for sustainable energy development and water resource management.

Abstract Studies have shown that the cachexia index (CXI) is a useful predictor of cachexia in patients with colorectal cancer. However, the application of the CXI is limited stemming from the intricacy and additional cost of radiographic examinations. This study aimed to develop an easy-to-use and practical CXI based on fat-free mass index (FFMI-CXI) to evaluate the prognostic value of FFMI-CXI in CRC. A total of 656 patients with CRC were enrolled in the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. The FFMI-CXI was calculated as [FFMI (kg)/height (m)2 × serum albumin (g/L)]/neutrophil-lymphocyte ratio. The cutoff value for FFMI-CXI was determined through the analysis of ROC curves and Youden’s index for both male and female cohorts. Kaplan–Meier survival curves with log-rank tests were conducted to compare time–event relationships between different groups. Cox proportional hazards regression models incorporating both univariate and multivariate variables were employed to explore the independent prognostic factors associated with OS. Logistic regression analysis was performed to assess the association of the FFMI-CXI with secondary outcomes. The major outcome was 5-year overall survival (OS). Based on the cutoff values, 331 patients had low FFMI-CXI, and 325 patients had high FFMI-CXI. Patients in the low FFMI-CXI subgroup were significantly older and had advanced TNM stage, malnutrition, high systemic inflammation, long hospitalizations, high hospitalization costs, adverse short-term outcomes, and all-cause mortality. Multivariate Cox regression analyses revealed that FFMI-CXI (HR 0.47, 95% CI 0.33–0.66; p

Two new species, Chlorocillium sinense and Calcarisporium guizhouense, isolated from a spider and fruiting body of Cordyceps sp., are introduced. Morphological comparisons and phylogenetic analyses based on multigene datasets (ITS+LSU+RPB2+tef-1alpha) support the establishment of the new species. A combined dataset of ITS, LSU, RPB2, and tef-1alpha showed the taxonomic placement of Chlorocillium in Clavicipitaceae for the first time. Pseudometarhizium is regarded as a synonym of Chlorocillium and two Pseudometarhizium species are transferred into the latter based on the phylogenetic analysis and morphological characteristics.

Abstract Background Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. Case presentation We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. Conclusions Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

Abstract As the COVID-19 pandemic has accelerated the shift towards mobile Internet while decreasing traditional, non-mobile Internet usage, understanding the implications of this trend on individuals’ subjective well-being has become particularly crucial. While the distinction in connectivity is evident, the specific ways in which each modality influences subjective well-being are not well documented. This study, grounded in the uses and gratifications theory, asserts that while both Internet types fulfil some similar gratifications, their unique gratifications lead to varying impacts on subjective well-being in normal and socially disruptive times. Utilising a representative longitudinal dataset from China comprising 46,803 observations from 15,601 individuals, our findings indicate that traditional Internet generally exerts a more positive influence on subjective well-being than mobile Internet. However, the role of mobile Internet has become significantly more pronounced during the COVID-19 pandemic. We further reveal the substitution effect between mobile and non-mobile Internet, which diminished during the COVID-19 pandemic. This study offers novel insights into the comparative effects of mobile and traditional Internet on subjective well-being, especially during social disturbances. This research contributes to a deeper understanding of technology’s role in enhancing subjective well-being, as well as in mitigating the impacts of crises.

Abstract Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.

Background: Our study aimed to examine the effects of COVID-19 on the physical fitness and academic performance of Chinese college students. Participants: The sample included physical fitness test data from 9,712 undergraduate students and academic performance data from 12,000 undergraduate students at a top university in China. Methods: Physical fitness was measured and evaluated according to the Chinese National Student Physical Fitness Standard. Data were analyzed using two-sample t-tests and Pearson product-moment correlations. Results: Total physical fitness test scores of college students decreased after the outbreak, but their mean body mass index (BMI) remained at normal levels. The mean academic performance of college students unexpectedly improved during the online learning period. The positive correlation between physical test scores and academic performance was significantly higher during COVID-19 than that before the outbreak. Conclusions: Chinese college students with high physical fitness during COVID-19 were more likely to achieve good academic performance.

Purpose: To introduce a modified Hughes procedure for the repair of large full-thickness defects of the lower eyelid. Methods: This retrospective study included 56 patients: 30 in the conventional group treated with a Hughes flap and 26 in the modified group treated with a full-thickness upper eyelid flap pedicled with levator aponeurosis, Muller muscle and conjunctiva. The reconstruction time, period of pedicle division and complication rates were evaluated. Results: The lower eyelid reconstruction time was 89.2±7.7 minutes in the conventional group and 61.7±7.5 minutes in the modified group, whereas the period of pedicle division was 21.1±3.0 days in the conventional group and 10.8±3.0 days in the modified group, and the differences were statistically significant (p = 0.000 and 0.000). Lower eyelid retraction was 0.4±0.4 mm in the conventional group and 0.1±0.2 mm in the modified group, and the difference was statistically significant (p = 0.001). Conclusion: The modified Hughes procedure in this study resulted in a shorter lower eyelid reconstruction time, a shorter period of pedicle division, and a lower degree of lower eyelid retraction. This technique is simple and convenient for reconstructing large full-thickness defects of the lower eyelid.

Purpose: To investigate the clinical features, radiographic features, treatment strategies, pathological features, and prognosis of orbital cholesterol granuloma (CG). Methods: Twelve patients with orbital CG who were referred to Tianjin Eye Hospital between January 2002 and December 2020 were included in this retrospective case series study. Data collected including patient ophthalmic manifestations, imaging findings, treatment strategies, pathological features, and prognosis were retrospectively reviewed. Results: The patients comprised 10 males and 2 females. The mean age was 34.5 years (standard deviation [SD] = 8.9, median: 36 and range: 16–45 years). Four patients had a history of orbital trauma. The clinical manifestations at the first visit were proptosis (7/12, 58.3%), periorbital or eyelid swelling (6/12, 50%), limitation of eye movement (4/12, 33.3%), ptosis (2/12, 16.7%), and decreased visual acuity (1/12, 8.3%). Computed tomography (CT) showed a nonenhancing, well-circumscribed lesion in the orbit with extensive erosion of the adjacent frontal bone and temporal bone. Magnetic resonance imaging (MRI) showed a nonenhancing mass with intermediate-to-high signal intensity on T1- and T2-weighted images. Ten patients underwent lateral orbitotomy, and two patients underwent supraorbital orbitotomy. All patients had aggressive bone erosion. Histopathologic evaluation of the cyst contents and wall revealed cholesterol clefts, multinucleated giant cells, histiocytes, foamy macrophages, and altered blood pigments. The mean follow-up time of 79.6 months (SD = 49.8, range: 19–193 months). Three patients were lost to follow-up. No postoperative diminution of vision was noted, and no recurrence was observed. Conclusions: CGs can present as superotemporal or temporal orbital lesions. The diagnosis can be established based on CT and MRI. Most of the patients can have no history of orbital trauma.

Abstract Purpose This study aimed to assess the prevalence of and factors associated with needle stick and sharps injuries (NSSIs) among health-care workers (HCWs) in a tertiary hospital in China. Materials and methods This retrospective survey was conducted with 562 HCWs at a tertiary hospital in China in July 2023. Information was collected using a self-designed questionnaire, and all enrolled members were required to fill in the demographic characteristics, occurrence of NSSIs and other associated factors in the past year. Logistic analysis was used to identify variables associated with NSSIs. Results The proportion of participants with at least one injury within the year preceding the investigation was 21.2%. Male (AOR = 2.116 [1.265, 3.538]), working hours per week > 40 (AOR = 1.718 [1.056,2.796]), rarely checking blood-borne infections before invasive operations (AOR = 2.219 [1.303,3.782]) were significantly associated with NSSIs. Conclusion The prevalence of NSSIs was not low in the survey area, especially in male, individuals with longer working hours, and rarely checking blood-borne infections before invasive operations. Therefore, it is necessary to promote educational programs to enhance awareness of standard prevention measures, especially for key populations, and reduce heavy workloads to decrease the occurrence of such injuries.

Abstract Objective This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. Methods Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. Results The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p

Abstract Background Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015–2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life’s Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. Results In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. Conclusion Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Abstract Background Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. Methods Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. Results After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. Conclusions The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Abstract Background To evaluate the performances of several advanced deep convolutional neural network models (AlexNet, VGG, GoogLeNet, ResNet) based on ensemble learning for recognizing chronic gingivitis from screening oral images. Methods A total of 683 intraoral clinical images acquired from 134 volunteers were used to construct the database and evaluate the models. Four deep ConvNet models were developed using ensemble learning and outperformed a single model. The performances of the different models were evaluated by comparing the accuracy and sensitivity for recognizing the existence of gingivitis from intraoral images. Results The ResNet model achieved an area under the curve (AUC) value of 97%, while the AUC values for the GoogLeNet, AlexNet, and VGG models were 94%, 92%, and 89%, respectively. Although the ResNet and GoogLeNet models performed best in classifying gingivitis from images, the sensitivity outcomes were not significantly different among the ResNet, GoogLeNet, and Alexnet models (p>0.05). However, the sensitivity of the VGGNet model differed significantly from those of the other models (p

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

Abstract The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain. Graphical Abstract

Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases.

Piperacillin is a beta-lactamase inhibitor frequently used in the treatment of urinary tract infections. It is a broad-spectrum antibiotic with strong antibacterial action against Pseudomonas aeruginosa and Enterobacter, especially extended-spectrum beta-lactamase-producing Enterobacteria and Enterococcus. Side effects of piperacillin include allergic reactions, rashes such as urticaria, leukopenia, interstitial nephritis, asthma attacks, serological reactions, candida infection, and bleeding with more severe reactions resulting in anaphylactic shock. Anemia and hemolytic anemia are rare adverse reactions to piperacillin, with an incidence of 0.01–0.10%. We report herein the case of a severe postoperative immune hemolytic reaction to piperacillin. Fortunately, we quickly recognized and identified the drug reaction caused by piperacillin, immediately stopped the use of piperacillin, and performed a blood transfusion. The patient recovered and was subsequently discharged from the hospital.

Objective To evaluate the effectiveness of dacryoendoscopic-assisted laser dacryoplasty with silicone intubation (DLDI) for the management of nasolacrimal duct obstruction (NLDO) or stenosis, and to identify the factors associated with DLDI failure.Methods and analysis This study was designed as a prospective, single-centre cohort study. Patients with NLDO or stenosis who underwent DLDI from December 2019 to December 2021 at Tianjin Eye Hospital were considered for enrolment. The Kaplan-Meier estimator was used to assess the anatomical and functional success rate of DLDI within 2 years follow-up after removal of the silicone stent. Cox proportional hazards regression models were used to identify risk factors for treatment failure.Results 170, 174 and 178 eyes were included in Groups A (proximal NLDO), B (distal NLDO) and C (nasolacrimal duct stenosis), respectively. The overall anatomical success rate was 84.8% for the entire cohort at the 2-year follow-up. The cumulative anatomical or functional success rate for Groups B and C was significantly higher than that for Group A. In the multivariable model, a higher risk of failed DLDI surgery was associated with a history of chronic dacryocystitis (HR=3.07; p

The great potential of polysaccharides in immunological regulation has recently been highlighted in pharmacological and clinical studies. Polysaccharides can trigger immunostimulatory responses through molecular identification, intra- and intercellular communication via direct or indirect interactions with the immune system. Various immunostimulatory polysaccharides or their derivative compounds interacts at cellular level to boost the immune system, including arabinogalactans, fucoidans, mannans, xylans, galactans, hyaluronans, fructans, pectin and arabinogalactans, etc. These natural polysaccharides are derived from various plants, animals and microbes. A unique structural diversity has been identified in polysaccharides, while monosaccharides and glucosidic bonds mainly confer diverse biological activities. These natural polysaccharides improve antioxidant capacity, reduce the production of pro-inflammatory mediators, strengthen the intestinal barrier, influence the composition of intestinal microbial populations and promote the synthesis of short-chain fatty acids. These natural polysaccharides are also known to reduce excessive inflammatory responses. It is crucial to develop polysaccharide-based immunomodulators that could be used to prevent or treat certain diseases. This review highlights the structural features, immunomodulatory properties, underlying immunomodulatory mechanisms of naturally occurring polysaccharides, and activities related to immune effects by elucidating a complex relationship between polysaccharides and immunity. In addition, the future of these molecules as potential immunomodulatory components that could transform pharmaceutical applications at clinical level will also be highlighted.

BackgroundEpithelioid hemangioendothelioma (EHE), is an uncommon, intermediate-grade malignant vascular tumor that can manifest in diverse organs, including the liver, lungs, and bones. Given its unique malignancy profile and rarity, there lacks a consensus on a standardized treatment protocol for EHE, particularly for hepatic epithelioid hemangioendothelioma (HEHE). This study aims to elucidate factors influencing the clinical prognosis of EHE by analyzing data from the SEER database, complemented with insights from a departmental cohort of 9 HEHE cases. Through this, we hope to shed light on potential clinical outcomes and therapeutic strategies for HEHE.MethodsUsing SEER data from 22 registries, we analyzed 313 liver cancer patients with ICD-O-3 9130 and 9133 histology. Twelve variables were examined using Cox regression and mlr3 machine learning. Significant variables were identified and compared. Clinical data, imaging characteristics, and treatment methods of nine patients from our cohort were also presented.ResultIn univariate and multivariate Cox regression analyses, Age, Sex, Year of diagnosis, Surgery of primary site, Chemotherapy, and Median household income were closely related to survival outcomes. Among the ten survival-related machine learning models, CoxPH, Flexible, Mboost, and Gamboost stood out based on Area Under the Curve(AUC), Decision Curve Analysis(DCA), and Calibration Curve Metrics. In the feature importance analysis of these four selected models, Age and Surgery of primary site were consistently identified as the most critical factors influencing prognosis. Additionally, the clinical data of nine patients from our cohort not only demonstrated unique imaging characteristics of HEHE but also underscored the importance of surgical intervention.ConclusionFor patients with resectable HEHE, surgical treatment is currently a highly important therapeutic approach.

PurposeCurrently, a range of electromagnetic therapies, including magnetic field therapy, micro-currents therapy, and tumor treating fields, are under investigation for their potential in central nervous system tumor research. Each of these electromagnetic therapies possesses distinct effects and limitations. Our focus is on overcoming these limitations by developing a novel electric field generator. This generator operates by producing alternating induced currents within the tumor area through electromagnetic induction.MethodsFinite element analysis was employed to calculate the distribution of electric fields. Cell viability was assessed using the CCK-8 assay. Tumor volumes and weights served as indicators to evaluate the effectiveness of TTIF. The in-vivo imaging system was utilized to confirm tumor growth in the brains of mice.ResultsTTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo.ConclusionTTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo. Consequently, TTIF emerges as a potential treatment option for patients with progressive or metastatic GBM.

A mechanism has been developed to achieve rapid deployment of longitudinally folding wings by utilizing compound actuation from the firing powder and the compressive spring. A theoretical model based on rigid-body dynamics was first proposed to study the deployment characteristics of longitudinal folding wings under compound-driven effects. Subsequently, deployment experiments were conducted using a prototype to validate the theoretical model. It was observed that the folding wings are deployed in 11 ms. Further parametric analysis indicates that the mass of both the propellant and the locking rod has a positive effect on the deploying velocity. However, the angular moment of inertia of folding wings has a negative effect on the initial angular velocity. This work can be helpful for designing the folding wing structures of missiles and aircrafts.

Intestinal microbiota and its metabolites are involved in many physiological processes of the human body and play a vital role in maintaining human health. The occurrence of kidney disease can cause intestinal microbiota imbalance, resulting in diarrhea. The change of intestinal microbiota and its metabolites content can aggravate renal function injury, which has a bidirectional regulating effect. The theory of renal-intestinal axis further clarified that the impaired renal function is related to the imbalance of intestinal microorganisms, and the impaired intestinal barrier is related to the accumulation of toxin products. Because of its unique therapeutic advantages, Traditional Chinese Medicine can treat diarrhea by enhancing the growth of beneficial bacteria, inhibiting pathogenic bacteria and immune regulation, and slow down the continuous deterioration of kidney disease. This paper focuses on the relationship between intestinal microbiota and its metabolites and diarrhea, the influence of Traditional Chinese Medicine on intestinal microbiota in the treatment of diarrhea, and the role of intestinal microbiota and its metabolites in the renal-intestinal axis. It provides a theoretical basis for Traditional Chinese Medicine to regulate intestinal microbiota and its metabolites based on the renal-intestinal axis theory to treat nephrology-induced diarrhea, and also provides a new idea and method for Traitional Chinese Medicine to treat nephrology-induced diarrhea.

ABSTRACT Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn’s disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens, Thermotalea metallivorans, Roseburia intestinalis, Dorea sp. AGR2135, Escherichia coli, Shigella sonnei, and Salmonella enterica, the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD.IMPORTANCESince previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn’s disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn’s Disease Activity Index (PCDAI). Crohn’s Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

Since the p53 protein is an important promising biomarker of lung tumor and colorectal tumor, it is very essential to design a highly effective mean to monitor the degree of p53 for the early clinical analysis/therapy of the related tumors. In this work, a sandwich-type electrochemical immunosensing (SES) platform is proposed for the first time to detect p53 via synthesizing Ti3C2Tx MXene nanoribbons (Ti3C2Tx Nb) and ferrocene/gold nanoparticles (Fc/Au) respectively as the sensing substrate and signal-amplifier. The superior electrical property and large surface area of Ti3C2Tx Nb are beneficial to assemble the initial p53-antibodies (Ab1), while the synthesized Fc/Au is devoted to assemble the secondary p53 antibodies (Ab2) and gives a magnified signal. By adopting the Fc molecules as the probes, the experiments reveal the response current of Fc resulted from the SES structure increases along with the p53 increase from 1.0 to 200.0 pg mL−1. A considerable low detection limit (1.0 pg mL−1) is achieved after optimizing several key conditions, it is thus confirmed the as-proposed SES mean exhibits significant application in the detection of p53 protein and other targets.

Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multi-disciplinary team (MDT) and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.

ABSTRACT Sugarcane yellow leaf virus (SCYLV) can reduce sugarcane productivity. A novel detection system based on reverse transcription-multienzyme isothermal rapid amplification (RT-MIRA) combined with CRISPR-Cas12a, named RT-MIRA-CRISPR-Cas12a, was developed. This innovative approach employs crude leaf extract directly as the reaction template, streamlining the extraction process for simplicity and speed. Combining RT-MIRA and CRISPR-Cas12a in one reaction tube increases the ease of operation while reducing the risk of aerosol contamination. In addition, it exhibits sensitivity equivalent to qPCR, boasting a lower detection limit of 25 copies. Remarkably, the entire process, from sample extraction to reaction completion, requires only 52–57 minutes, just a thermostat water bath. The result can be observed and judged by the naked eye.IMPORTANCESugarcane yellow leaf disease (SCYLD) is an important viral disease that affects sugarcane yield. There is an urgent need for rapid, sensitive, and stable detection methods. The reverse transcription-multienzyme isothermal rapid amplification combined with CRISPR-Cas12a (RT-MIRA-CRISPR-Cas12a) method established in this study has good specificity and high sensitivity. In addition, the system showed good compatibility and stability with the crude leaf extract, as shown by the fact that the crude extract of the positive sample could still be stably detected after 1 week when placed at 4°C. RT-MIRA-CRISPR-Cas12a, reverse transcription polymerase chain reaction (RT-PCR), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect SCYLV on 33 sugarcane leaf samples collected from the field, and it was found that the three methods reached consistent conclusions. This Cas12a-based detection method proves highly suitable for the rapid on-site detection of the SCYLV.

In this paper, a dual deep Q-network (DDQN) energy management model based on long-short memory neural network (LSTM) speed prediction is proposed under the model predictive control (MPC) framework. The initial learning rate and neuron dropout probability of the LSTM speed prediction model are optimized by the genetic algorithm (GA). The prediction results show that the root-mean-square error of the GA-LSTM speed prediction method is smaller than the SVR method in different speed prediction horizons. The predicted demand power, the state of charge (SOC), and the demand power at the current moment are used as the state input of the agent, and the real-time control of the control strategy is realized by the MPC method. The simulation results show that the proposed control strategy reduces the equivalent fuel consumption by 0.0354 kg compared with DDQN, 0.8439 kg compared with ECMS, and 0.742 kg compared with the power-following control strategy. The difference between the proposed control strategy and the dynamic planning control strategy is only 0.0048 kg, 0.193%, while the SOC of the power battery remains stable. Finally, the hardware-in-the-loop simulation verifies that the proposed control strategy has good real-time performance.