gutMDisorder v2.0: a comprehensive database for dysbiosis of gut microbiota in phenotypes and interventions.

Gut microbiota plays a significant role in maintaining host health, and conversely, disorders potentially lead to dysbiosis, an imbalance in the composition of the gut microbial community. Intervention approaches, such as medications, diets, and several others, also alter the gut microbiota in either a beneficial or harmful direction. In 2020, the gutMDisorder was developed to facilitate researchers in the investigation of dysbiosis of gut microbes as occurs in various disorders as well as with therapeutic interventions. The database has been updated this year, following revision of previous publications and newly published reports to manually integrate confirmed associations under multitudinous conditions. Additionally, the microbial contents of downloaded gut microbial raw sequencing data were annotated, the metadata of the corresponding hosts were manually curated, and the interactive charts were developed to enhance visualization. The improvements have assembled into gutMDisorder v2.0, a more advanced search engine and an upgraded web interface, which can be freely accessed via http://bio-annotation.cn/gutMDisorder/.

Confining Nano-ZrO2 in Nanodomains Leads to Electroactive Artificial Muscle with Large Deformation.

Dielectric elastomers generate muscle-like electroactive actuation, which is applicable in soft machines, medical devices, etc. However, the actuation strain and energy density of most dielectric elastomers, in the absence of prestretch, have long been limited to ∼20% and ∼10 kJ m-3, respectively. Here, we report a dielectric elastomer with ZrO2 nanoparticles confined in nanodomains, which achieves an actuation strain >100% and an energy density of ∼150 kJ m-3 without prestretch. We decorate the surface of each nanoparticle with a layer of a diblock oligomer, poly(acrylic acid-b-styrene). The surface-decorated nanoparticles coassemble with a triblock copolymer elastomer, poly(styrene-b-(2-ethylhexyl acrylate)-b-styrene) during cosolvent casting. Consequently, the nanoparticles are confined in the polystyrene nanodomains, which results in a dielectric elastomer nanocomposite with a low modulus, high breakdown strength, and intense strain-hardening behavior. During the actuation, the nanocomposite avoids the snap-through instability that most elastomers would suffer and achieves a superior actuation performance.

Ultra-high b-value DWI accurately identifies isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas.

OBJECTIVES: To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI). MATERIALS AND METHODS: This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADCb500/b1000, ADCb500/b2000, ADCb500/b3000, ADCb500/b4000, ADCb500/b6000, ADCb500/b8000, and ADCb500/b10000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared. RESULTS: All ADCs were significantly higher in IDH mutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADCb500/b8000 had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADCb500/b1000 were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADCb500/b8000 and ADCb500/b10000 were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADCb500/b6000 when distinguishing glioblastoma from astrocytoma, 0.979 for ADCb500/b8000 and ADCb500/b10000 when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADCb500/b10000 when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all). CONCLUSION: Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria. CLINICAL RELEVANCE STATEMENT: Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma. KEY POINTS: • Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.

gutMGene: a comprehensive database for target genes of gut microbes and microbial metabolites.

gutMGene (http://bio-annotation.cn/gutmgene), a manually curated database, aims at providing a comprehensive resource of target genes of gut microbes and microbial metabolites in humans and mice. Metagenomic sequencing of fecal samples has identified 3.3 × 106 non-redundant microbial genes from up to 1500 different species. One of the contributions of gut microbiota to host biology is the circulating pool of bacterially derived small-molecule metabolites. It has been estimated that 10% of metabolites found in mammalian blood are derived from the gut microbiota, where they can produce systemic effects on the host through activating or inhibiting gene expression. The current version of gutMGene documents 1331 curated relationships between 332 gut microbes, 207 microbial metabolites and 223 genes in humans, and 2349 curated relationships between 209 gut microbes, 149 microbial metabolites and 544 genes in mice. Each entry in the gutMGene contains detailed information on a relationship between gut microbe, microbial metabolite and target gene, a brief description of the relationship, experiment technology and platform, literature reference and so on. gutMGene provides a user-friendly interface to browse and retrieve each entry using gut microbes, disorders and intervention measures. It also offers the option to download all the entries and submit new experimentally validated associations.

Mobility, speciation of cadmium, and bacterial community composition along soil depths during microbial carbonate precipitation under simulated acid rain.

An overexploitation of earth resources results in acid deposition in soil, which adversely impacts soil ecosystems and biodiversity and affects conventional heavy metal remediation using immobilization. A series of column experiments was conducted in this study to compare the cadmium (Cd) retention stability through biotic and abiotic carbonate precipitation impacted by simulated acid rain (SAR), to build a comprehensive understanding of cadmium speciation and distribution along soil depth and to elucidate the biogeochemical bacteria-soil-heavy metal interfaces. The strain of Sporosarcina pasteurii DSM 33 was used to trigger the biotic carbonate precipitation and cultivated throughout the 60-day column incubation. Results of soil pH, electrical conductivity (EC), and quantitative CdCO3/CaCO3 analysis concluded that the combination of biotic and abiotic soil treatment could reinforce soil buffering capacity as a strong defense mechanism against acid rain disturbance. Up to 1.8 ± 0.04 U/mg urease enzyme activity was observed in combination soil from day 10, confirming the sustained effect of urease-mediated microbial carbonate precipitation. Cadmium speciation and distribution analyses provided new insights into the dual stimulation of carbonate-bound and Fe/Mn-bound phases of cadmium immobilization under microbially induced carbonate precipitation (MICP). As confirmed by the microbial community analysis, outsourcing urea triggered diverse microbial metabolic responses, notably carbonate precipitation and dissimilatory iron metabolism, in both oxygen-rich topsoil and oxygen-depleted subsurface layers. The overall investigation suggests the feasibility of applying MICP for soil Cd remediation under harsh environments and stratagem by selecting microbial functionality to overcome environmental challenges.

NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production.

In the setting of virus infection, autophagy regulates the synthesis of type I interferon (IFN) via multiple mechanisms to prevent adverse overreaction. Interferon regulatory factor (IRF) 3, the dominant transcriptional factor of type I IFN, can be degraded via autophagy-lysosomal pathway. However, the exact regulatory mechanism is not yet well elucidated. IRF3 was targeted into autophagosome by interacting with cargo receptors including p62, NDP52 and NBR1. The recent studies have reported the mechanism of p62 and NDP52 sequestrating IRF3. This work aims to investigate the role of NBR1 in the process of IRF3 degradation. We found that blocking autophagy via ATG3/ATG7 knockout and chemical inhibitors both resulted in the accumulation of IRF3 protein and increased synthesis of type I IFN, while enhancing autophagy activity led to more obvious clearance of IRF3 in HEK293T cells infected with Sendai virus (SeV). Our data suggested that NBR1 bound both unphosphorylated and phosphorylated IRF3 through its ubiquitin-associated domain. Meanwhile, viral infection elevated the expression of NBR1, which sequentially formed a negative feedback loop to promote IRF3 degradation and hence optimized the type I IFN signaling. This study expands the knowledge of molecular mechanisms regulating the IRF3 stability and function during viral infection.

Sodium glutamate as a booster: Inducing Rhodosporidium paludigenum to enhance the inhibition of Penicillium expansum on pears.

AIMS: This research sought to improve the ability of biocontrol yeast to suppress postharvest fungal disease and explore possible mechanisms of action. METHODS AND RESULTS: The addition of 2% sodium glutamate (SG), which is edible and recognized as safe, enhances the inhibitory effect of Rhodosporidium paludigenum Fell & Tallman on Penicillium expansum in vivo and in vitro. Rhodosporidium paludigenum cells grown in medium with a final concentration of 2% SG, displayed viability under a variety of stress conditions, including sodium chloride (NaCl), calcofluor white (CFW), Congo red (CR) and sodium dodecyl sulphate (SDS). Activity and relative gene expression levels of antioxidant-related enzymes in R. paludigenum, including peroxisomal catalase (CAT), thioredoxin reductase (TrxR), glutathione peroxidase (GSH-PX), glutathione reductase (GR) and superoxide dismutase (SOD) were altered in the presence of SG. Levels of reactive oxygen species (ROS) increased in cells grown in the presence of SG as well as the content of several amino acids. CONCLUSIONS: In the presence of 2% SG R. paludigenum inhibited P. expansum and exhibited tolerance to a number of stressful conditions which may involve the upregulation of antioxidant enzymes and amino acids. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability of culture conditions to enhance the fungal suppressive abilities of yeast has the potential to enhance the management of postharvest disease in fruit.

Secretions released from mesenchymal stem cells improve spermatogenesis restoration of cytotoxic treatment with busulfan in azoospermia mice.

This study aimed at the efficacy of sequential treatment of bone marrow-derived mesenchymal stem cell secretion for busulfan-treated azoospermia in mice. The conditioned media (CM) was obtained from bone marrow mesenchymal stem cells (MSCs) or 293 cells. Chemically induced azoospermia mice received 200 µl MSC-CM or 293-CM twice a week intravenously for three consecutive weeks. The histological assessment of spermatogenic recovery quantifying the expression of meiosis-associated genes, and Sertoli cell barrier functional factors were assessed. The characteristics of TM4 cells (Sertoli cell line) after pre-incubation of MSC-CM in vitro were also obtained. The MSC-CM group had the most spermatogenic colonies among the three groups (p < .05), but no spermatids were seen. Expressions of the meiosis-associated genes Dazl, Vasa, Miwi, Stra8, CyclinA1, Pgk2 and Scp3 in MSC-CM testis were remarkably higher compared with 293-CM and busulfan groups respectively (p < .05). The levels of Sertoli cell barrier functional factors, for example ICAM-1 and N-cadherin, were significantly increased during MSC-CM treatment (p < .05). Moreover, pre-incubation of MSC-CM particularly accelerated the CD54 (ICAM-1) and CD44 expressions of TM4 cells and promoted cell inherent adhesion. MSC-CM treatment can significantly improve the short-term restoration of spermatogonial structures of chemically induced azoospermia related to facilitating Sertoli cell adhesion integrity.

Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc). The structure of BAT was examined by hematoxylin and eosin staining and immunohistochemical analysis. The glucose uptake in BAT was measured in vivo by [18F]-fluoro-2-deoxyglucose-micro-positron emission tomography. The gene expression in BAT was determined by real-time PCR, and the 5'-C-phosphate-G-3' site-specific methylation was quantitatively analyzed. Intrauterine hyperglycemia exposure resulted in the impaired structure of BAT and decreased glucose uptake function in BAT in adulthood. The expressions of the genes involved in thermogenesis and mitochondrial respiratory chain in BAT, such as Ucp1, Cox5b, and Elovl3, were down-regulated by intrauterine hyperglycemia exposure at 18.5 dpc and at 16 wk of age. Furthermore, higher methylation levels of Ucp1, Cox5b, and Elovl3 were found in offspring of mothers with streptozotocin-induced diabetes. Our results provide the evidence for enduring inhibitory effects of intrauterine hyperglycemia on BAT development in offspring. Intrauterine hyperglycemia is associated with increased DNA methylation of the BAT specific genes in offspring, which support an epigenetic involvement.-Yu, D.-Q., Lv, P.-P., Yan, Y.-S., Xu, G.-X., Sadhukhan, A., Dong, S., Shen, Y., Ren, J., Zhang, X.-Y., Feng, C., Huang, Y.-T., Tian, S., Zhou, Y., Cai, Y.-T., Ming, Z.-H., Ding, G.-L., Zhu, H., Sheng, J.-Z., Jin, M., Huang, H.-F. Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson's Disease: Synaptic Pathology and Neuronal Aging.

The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKß-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD.

Efficient biodegradation of organic matter using a thermophilic bacterium and development of a cost-effective culture medium for industrial use.

Microorganisms with efficient organic matter degradation ability are essential for organic waste treatment. In this study, a thermophilic bacterium, Bacillus thermoliquefaciens, was identified to have excellent cellulase, amylase, and protease activity, and provided efficient degradation of food waste. This is the first report on the organic matter degradation potential of B. thermoliquefaciens. Using a "one-variable-at-a-time" approach and response surface methodology, the optimal culture conditions for B. thermoliquefaciens were determined to be a 5% inoculation level, 50 °C culture temperature, 25 mL filling volumes in 250 mL flasks, and 180 rpm shaking for 24 h. The optimized medium was formulated as 1 g Na2HPO4, 1 g KH2PO4, 0.05 g MgSO4, 3 g NaCl, 0.05 g CaCl2, 11.44 g wheat bran powder, 4.92 g soybean meal, and 1 L distilled water at pH 7.12. The maximum biomass attained was 1.57 ± 0.153 × 109 CFU/mL. The cost of this medium was 4.18 times less than that before optimization. This promising result lays a foundation for future industrial application of this bacterium to the degradation of organic waste.

Mesenchymal stem cell-secreted factors delayed spermatogenesis injuries induced by busulfan involving intercellular adhesion molecule regulation.

The present study was designed to investigate the therapeutic effect of bone marrow MSC-derived factors on gonadotropic toxicity induced by busulfan in vivo. The conditioned media (CM) was obtained from MSCs in serum-free incubation for 48 hr and concentrated ~25-fold by ultrafiltration. The CM of HEK 293 cells was treated as control (293-CM). MSC-CM was injected into busulfan mice via caudal veins after 1 day of busulfan treatment for 2 weeks (200 µl per dose/twice weekly）. Compared to the 293-CM group, testicular injury was delayed in MSC-CM group, including reduced vacuolations of cells in the basal compartment of the seminiferous epithelium and detachment of cells from basement membrane. Apoptotic spermatogenic cells were significantly decreased in MSC-CM group (p ï¼œ 0.05). Interesting N-cadherin，ICAM-1 and P-cadherin expressions significantly increased in MSC-CM group, while occludin, ZO-1 and connexin 43 expressions showed no difference among MSC-CM, 293-CM and busulfan groups. Present results suggest MSC-secreted factors protect spermatogenesis impairment after busulfan treatment by reducing the apoptosis of spermatogenic cells and enhancing intercellular adhesion molecule expressions.

Vasodilator-stimulated phosphoprotein (VASP), a novel target of miR-4455, promotes gastric cancer cell proliferation, migration, and invasion, through activating the PI3K/AKT signaling pathway.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs which play important roles in the carcinogenesis of gastric cancer (GC). Expression profiling of miRNAs in paired gastric cancer and adjacent normal gastric tissues has demonstrated that miR-4455 is down-regulated in gastric cancer tissues, but its functional role in the carcinogenesis of GC had not previously been investigated. AIMS: The purpose of this study was to investigate the functional and biological mechanisms of miR-4455 in the progression of GC, in vitro. METHODS: Expression of miR-4455 was compared in human GC tissue samples and paired adjacent normal tissue samples. The in vitro effects of miR-4455 expression in MGC-803 cells on their proliferation, invasion, and migration were assessed by MTT assays and 5-bromo-2'-deoxyuridine staining, matrigel-invasion analysis and wound healing assays. Bioinformatics analysis (using PicTar, target scan and miRBase target) was used to identify potential targets for miR-4455, and the luciferase reporter assay, qRT-PCR and Western-blotting analyses were used to confirm VASP as the target of miR-4455. In addition, the effects of downregulation of VASP on the activation of PI3K/AKT signaling pathway were measured using Western-blot analysis. RESULTS: The expression of miR-4455 was markedly down-regulated in gastric cancer tissues vs. adjacent normal tissues, and miR-4455 expression inhibited the proliferation, invasion and migration of MGC-803 GC cells in vitro. Luciferase reporter assays revealed that miR-4455 inhibited VASP expression by targeting the 3'-UTR sequence of VASP. Furthermore, silencing of VASP markedly inhibited the activation of the PI3K/AKT signaling pathway. CONCLUSION: Our results suggest that miR-4455 functions as a tumor suppressor in gastric cancer, by targeting VASP leading to activation of the PI3K/AKT signaling pathway and the inhibition of VASP mediated proliferation, migration and invasion of gastric cancer cells.

CaSK23, a Putative GSK3/SHAGGY-Like Kinase of Capsicum annuum, Acts as a Negative Regulator of Pepper's Response to Ralstonia solanacearum Attack.

GSK3-like kinases have been mainly implicated in the brassinosteroids (BR) pathway and, therefore, in plant growth, development, and responses to abiotic stresses; however, their roles in plant immunity remain poorly understood. Herein, we present evidence that CaSK23, a putative GSK3/SHAGGY-like kinase in pepper, acts as a negative regulator in pepper's response to Ralstonia solanacearum (R. solanacearum) inoculation (RSI). Data from quantitative RT-PCR (qRT-PCR) showed that the constitutively-expressed CaSK23 in pepper leaves was down-regulated by RSI, as well as by exogenously-applied salicylic acid (SA) or methyl jasomonate (MeJA). Silencing of CaSK23 by virus-induced gene silencing (VIGS) decreased the susceptibility of pepper plants to RSI, coupled with up-regulation of the tested genes encoding SA-, JA-, and ethylene (ET)-dependent pathogenesis-related (PR) proteins. In contrast, ectopic overexpression (OE) of CaSK23 conferred a compromised resistance of tobacco plants to RSI, accompanied by down-regulation of the tested immunity-associated SA-, JA-, and ET-dependent PR genes. In addition, transient overexpression of CaSK23 in pepper plants consistently led to down-regulation of the tested SA-, JA-, and ET-dependent PR genes. We speculate that CaSK23 acts as a negative regulator in pepper immunity and its constitutive expression represses pepper immunity in the absence of pathogens. On the other hand, its decreased expression derepresses immunity when pepper plants are attacked by pathogens.

[Neuroprotective effect of rapamycin against Parkinson's disease in mice].

OBJECTIVE: To investigate the effect of rapamycin on Parkinson's disease (PD) and its underlying mechanism in mice. METHODS: Sixty SPF adult male C57BL/6 mice were randomly divided into control group, model group and treatment group. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) was used to induce Parkinson's disease in model group and treatment group. All mice were trained to cross the runway and were subjected to computer-assisted CatWalk. The numbers of tyrosine hydroxylase positive (TH+) neurons in the substantia nigra (SN) were assessed by unbiased stereology using the optical fractionator method; protein expression was detected by Western blot analysis; and glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by spectrophotometry. RESULTS: In the model group, a decrease in stride rate and an increase in variation of stance and swing were noted by CatWalk system (P<0.05 or P<0.01); the numbers of TH+ neurons decreased (P<0.01); expression of p-Akt, p-S6K, p-S6 and p-ULK increased (all P<0.01); LC3-Ⅱ/Ⅰ ratio decreased (P<0.01); MDA level was elevated while the levels of SOD and GSH-PX were reduced (all P<0.01). Compared with the model group, after treated with rapamycin, the abnormal behavior including the stride length, variation of stance and swing and step patterns induced by MPTP were all improved (P<0.05 or P<0.01); the numbers of TH+ neurons increased (P<0.05); the expression of p-Akt, p-S6K, p-S6 and p-ULK was suppressed (all P<0.01); the LC3-Ⅱ/Ⅰ ratio was upregulated (P<0.05); MDA level decreased while the levels of GSH-Px and SOD increased (all P<0.01). CONCLUSIONS: Rapamycin inhibits the activation of mTOR pathway, which contributes to protect against the loss of dopaminergic neurons and provide behavioral improvements in mice with Parkinson's disease. These results are partially related to the ability of rapamycin in inducing autophagy and reducing oxidative stress.

Dynamic imaging of autophagy-lysosomal pathway and autophagy function following pulmonary hypoxia/reoxygenation in vitro.

Alterations of the autophagy-lysosomal pathway (ALP) and autophagy have been involved in lung ischemia-reperfusion (I/R) injury. However, dynamic imaging of ALP function under lung I/R injury particularly is not fully understood. Here we depicted the live-cell fluorescence imaging of autophagosome to monitor ALP activation and autophagy function. The pAsRed2-N1-LC3 vectors were transfected into CRL-2192 NR8383 (an alveolar macrophage cell line) and CCL149 (an alveolar epithelial cell line) successfully. 0-h, 2-h, 4-h, and 6-h hypoxia/0-h, 2-h, 4-h, and 6-h reoxygenation were then induced with an ALP inhibitor (3-MA) or activator (rapamycin) in the culture of transfected cells separately. ALP activation was conformed by up-regulating AMPK and beclin1 expression. Apoptosis was not obvious in 2-h hypoxia/2-h reoxygenation. pAsRed2-N1-LC3 CCL149 and pAsRed2-N1-LC3 NR8383 cells revealed gradually enhanced AsRed2 from 2-h to 6-h hypoxia/reoxygenation. AsRed2 varied sensitively to 3-MA and rapamycin interventions during 2-h hypoxia/reoxygenation. Our data provides a simple method of autophagosome imaging to monitor ALP activation and autophagy function in lung I/R injury.

Clinical study: the impact of goal-directed fluid therapy on volume management during enhanced recovery after surgery in gastrointestinal procedures.

Background: Goal-directed fluid therapy, as a crucial component of accelerated rehabilitation after surgery, plays a significant role in expediting postoperative recovery and enhancing the prognosis of major surgical procedures. Methods: In line with this, the present study aimed to investigate the impact of target-oriented fluid therapy on volume management during ERAS protocols specifically for gastrointestinal surgery. Patients undergoing gastrointestinal surgery at our hospital between October 2019 and May 2021 were selected as the sample population for this research. Results: 41 cases of gastrointestinal surgery patients were collected from our hospital over 3 recent years. Compared with T1, MAP levels were significantly increased from T2 to T5; cardiac output (CO) was significantly decreased from T2 to T3, and significantly increased from T4 to T5; and SV level was significantly increased from T3 to T5. Compared with T2, HR and cardiac index (CI) were significantly elevated at T1 and at T3-T5. Compared with T3, SVV was significantly decreased at T1, T2, T4, and T5; CO and stroke volume (SV) levels were increased significantly at T4 and T5. In this study, pressor drugs were taken for 23 days, PACU residence time was 40.22 ± 12.79 min, time to get out of bed was 12.41 ± 3.97 h, exhaust and defecation time was 18.11 ± 7.52 h, and length of postoperative hospital stay was 4.47 ± 1.98 days. The average HAMA score was 9.11 ± 2.37, CRP levels were 10.54 ± 3.38 mg/L, adrenaline levels were 132.87 ± 8.97 ng/L, and cortisol levels were 119.72 ± 4.08 ng/L. Prealbumin levels were 141.98 ± 10.99 mg/L at 3 d after surgery, and 164.17 ± 15.84 mg/L on the day of discharge. Lymphocyte count was 1.22 ± 0.18 (109/L) at 3 d after surgery, and 1.47 ± 0.17 (109/L) on the day of discharge. Serum albumin levels were 30.51 ± 2.28 (g/L) at 3 d after surgery, and 33.52 ± 2.07 (g/L) on the day of discharge. Conclusion: Goal-directed fluid therapy (GDFT) under the concept of Enhanced Recovery After Surgery (ERAS) is helpful in volume management during radical resection of colorectal tumors, with good postoperative recovery. Attention should be paid to the influence of pneumoperitoneum and intraoperative posture on GDFT parameters.

An optimized non-T cell transfection system based on HEK293FT cells for CD3ζ phosphorylation and ubiquitination.

CD3ζ is part of the T cell receptor (TCR)/CD3 complex that plays a critical role in antigen recognition and subsequent T cell activation. Understanding the mechanisms that regulate CD3ζ can provide new insights into the T cell-mediated immune responses. However, it is challenging to deliver exogenous genes into T cells for functional and mechanistic analyses. To this end, we established a non-T cell transfection system based on HEK293FT cells to screen for candidate regulatory proteins. The transfection was optimized using relatively high confluent cultures and the transfection reagent PolyJet™. Pervanadate (PV) treatment sustained tyrosine phosphorylation of CD3ζ, and facilitated the subsequent activation-dependent ubiquitination by E3 ligase Cbl-b in the HEK293FT system. Lck and Zap70 kinases enhanced the levels of phosphorylated CD3ζ in the presence of PV. We compared the effects of E3 ligases and the corresponding adaptor proteins on activation-dependent ubiquitination of CD3ζ in the PV-stimulated cells, and found that Cbl-b was most effective. Taken together, we have demonstrated that a non-T cell transfection system based on PV-treated HEK293FT cells could effectively mimic CD3ζ phosphorylation and ubiquitination and is a promising model for studying the role of CD3ζ signaling in T cell activation.

A retrospective study to determine the correlation among HBV PreS1 antigen, HBV e antigen, alanine aminotransferase, and HBV DNA.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection presents with indicators of varying clinical significance. We aimed to evaluate the correlation among HBV Pre-S1 antigen (HBV PreS1-Ag), HBV e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT) levels. METHODS: We retrospectively analyzed 6180 serum samples collected between 2020 and 2022 at the Shanghai General Hospital, China. Data regarding PreS1-Ag, HBeAg, ALT, and HBV DNA were compiled. Correlation analyses and cross-tabulations were employed to explore the diagnostic indicators. RESULTS: The detection rates of both antigen indicators showed a proportional increase with HBV DNA loads. The correlation between PreS1-Ag and HBV DNA (r = 0.616) was stronger than that between HBeAg and HBV DNA (r = 0.391). The specificity of PreS1-Ag (84.30 %) was lower than that of HBeAg (97.44 %), whereas the sensitivity of HBeAg (91.13 %) significantly surpassed that of PreS1-Ag (29.56 %). Among the HBV DNA positive patients, 92.04 % tested positive for at least one indicator, which exceeded the rate of PreS1+HBeAg- and PreS1-HBeAg+ (52. 28 % and 68. 56 %, respectively). Only 1.75 % of the patients exhibited double negativity, which was lower than the percentage of patients with single negativity (1.95 % and 12.00 % for PreS1-Ag and HBeAg, respectively). The PreS1 levels correlated with ALT levels (r = 0.317); patients with PreS1-positive status had higher ALT levels than patients with PreS1-negative status. CONCLUSION: PreS1-Ag is a more robust HBV replication indicator than HBeAg. PreS1-Ag displayed high sensitivity, whereas HBeAg demonstrated high specificity. Moreover, PreS1-Ag levels correlated with ALT levels. A combination of these indicators demonstrated dependable clinical value for detecting HBV infection and evaluating liver function.

Emission characteristics of carbonyl compounds from open burning of typical subtropical biomass in South China.

Open biomass burning (OBB) is one of the largest primary emission sources for atmospheric carbonyl compounds, key precursors for ozone and secondary organic aerosol pollution. To clarify the carbonyl emissions, the comprehensive characteristics of C1-C10 carbonyl compounds from open burning of seven typical subtropical biomass in China were investigated in this study, which included subtropical plants and agricultural residues. Total 27 carbonyl compounds were detected. The total EFs were 2824 mg kg-1 with 95% confidence interval (CI) [2418, 3322] for burning subtropical plants and 4080 mg kg-1 with 95% CI [3446, 4724] for burning agriculture residues, respectively. The EFs were 2-3 orders of magnitude larger than previous values in China. Aliphatic aldehydes were the largest group of carbonyl groups, with acetaldehyde, as the most abundant carbonyl species (about 30% contribution). Formaldehyde, acetone, acrolein, glyoxal, methylglyoxal, butanone, isovaleraldehyde, and m-tolualdehyde were also found to be abundant and varying with the types of biomass burnt. Formaldehyde emission ratios to acetonitrile and CO were lower than those in previous studies both for burning plants and agricultural residues. There were significant variabilities in the emission ratios and factors among different types of OBBs. Strong positive correlations were found between carbonyl emissions and CO emissions and water content in biomass; furthermore, total carbonyl concentrations measured in the flaming stage were higher than those in the smoldering one. This study provides important fundamental measurement data on carbonyl emissions from burning typical subtropical plants and agricultural residues, which will help improve the quality of emission inventories and better understand the potential impacts of OBB on regional air quality in southern China.