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In order to evaluate the safety and probiotic properties of Lactobacillus plantarum HCS03-001(CGMCC No.16258), the safety of Lactobacillus plantarum HCS03-001 was evaluated by hemolysis test, drug resistance test and acute transoral toxicity test. The probiotic properties of the strain were evaluated by acid and bile salt tolerance test, bacteriostatic functional properties test and laxative efficacy test. The results showed that Lactobacillus plantarum HCS03-001 did not form transparent circle on the Colombian blood finger culture medium, that was, there was no hemolysis. Lactobacillus plantarum HCS03-001 was sensitive to penicillin (PEN), ampicillin (AM), imipenem (IP), meropenem (MP), linezolid (LZ), and datoramycin (DPC), and neutral to erythromycin (EM) and resistant to vancomycin (VA). The acute oral toxicology of mice was non-toxic, and the strain was confirmed to be safe to eat.The survival rate of the strain was 94.29% and 92.33% at pH3.0 and pH2.0 for 3 h, respectively. The survival rate could still reach 88.82% at 1.5 g/L bile salt for 3 h. It had inhibitory effect on intestinal and oral pathogens (Porphyromonas gingivalis and Streptococcus mutans). It had a good effect on promoting defecation in constipation model of loperamide hydrochloride. Lactobacillus plantarum HCS03-001 has good safety and probiotics.

Abstract The traditional method for analyzing the content of instant tea has disadvantages such as complicated operation and being time-consuming. In this study, a method for the rapid determination of instant tea components by near-infrared (NIR) spectroscopy was established and optimized. The NIR spectra of 118 instant tea samples were used to evaluate the modeling and prediction performance of a combination of binary particle swarm optimization (BPSO) with support vector regression (SVR), BPSO with partial least squares (PLS), and SVR and PLS without BPSO. Under optimal conditions, Rp for moisture, caffeine, tea polyphenols, and tea polysaccharides were 0.9678, 0.9757, 0.7569, and 0.8185, respectively. The values of SEP were less than 0.9302, and absolute values of Bias were less than 0.3667. These findings indicate that machine learning can be used to optimize the detection model of instant tea components based on NIR methods to improve prediction accuracy.

Spinal cord injury (SCI) is defined as damage to the spinal cord that temporarily or permanently changes its function. There is no definite treatment established for neurological complete injury patients. This study investigated the effect of ginseng extract and ginsenosides on neurological recovery and antioxidant efficacies in rat models following SCI and explore the appropriate dosage. Searches were done on PubMed, Embase, and Chinese databases, and animal studies matches the inclusion criteria were selected. Pair-wise meta-analysis and subgroup analysis were performed. Ten studies were included, and the overall methodological qualities were low quality. The result showed ginseng extract and ginsenosides significantly improve neurological function, through the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale (pooled MD = 4.40; 95% CI = 3.92 to 4.88; p

BackgroundStructural autografts harvested from the iliac bone have been used in atlantoaxial fusion; they have been the gold standard for years. However, emerging occipital bone grafts have the advantage of avoiding donor-site morbidity and complications. Thus, we compared the clinical outcomes of structural autografts from the occipital bone or iliac crest and discussed the clinical significance of occipital bone grafts in pediatric patients.MethodsPediatric patients who underwent posterior fusion using occipital bone grafts (OBG) or iliac bone grafts (IBG) between 2017 and 2021 were included in this study. Data on clinical outcomes, including operation time, estimated blood loss, length of hospitalization, complications, fusion rate, and fusion time, were collected and analyzed. Additionally, 300 pediatric patients who underwent cranial computed tomography scans were included in the bone thickness evaluation procedure. The central and edge thicknesses of the harvested areas were recorded and analyzed.ResultsThirty-nine patients were included in this study. There were no significant differences in patient characteristics between the OBG and IBG groups. Patients in both groups achieved a 100% fusion rate; however, the fusion time in the OBG group was significantly longer than that in the IBG group. Estimated blood loss, operation time, and length of hospitalization were significantly lower in the OBG group than those in the IBG group. The surgery-related complication rate was lower, but not significantly, in the OBG group than that in the IBG group. For occipital bone thickness evaluation, a significant difference in the central part of the harvesting area was found between the young and old groups, with no significant sex differences.ConclusionThe use of OBG for atlantoaxial fusion is acceptable for pediatric patients with atlantoaxial dislocation, avoiding donor-site morbidity and complications.

Introduction: Maternal immune activation (MIA) is closely related to the onset of autism-like behaviors in offspring, but the mechanism remains unclear. Maternal behaviors can influence offspring’s development and behaviors, as indicated in both human and animal studies. We hypothesized that abnormal maternal behaviors in MIA dams might be other factors leading to delayed development and abnormal behaviors in offspring.Methods: To verify our hypothesis, we analyzed poly(I:C)-induced MIA dam’s postpartum maternal behavior and serum levels of several hormones related to maternal behavior. Pup’s developmental milestones and early social communication were recorded and evaluated in infancy. Other behavioral tests, including three-chamber test, self-grooming test, open field test, novel object recognition test, rotarod test and maximum grip test, were performed in adolescence of pups.Results: Our results showed that MIA dams exhibit abnormal static nursing behavior but normal basic care and dynamic nursing behavior. The serum levels of testosterone and arginine vasopressin in MIA dams were significantly reduced compared with control dams. The developmental milestones, including pinna detachment, incisor eruption and eye opening, were significantly delayed in MIA offspring compared with control offspring, while the weight and early social communication showed no significant differences between the two groups. Behavioral tests performed in adolescence showed that only male MIA offspring display elevated self-grooming behaviors and reduced maximum grip.Discussion: In conclusion, MIA dams display abnormal postpartum static nursing behavior concomitantly with reduced serum levels of testosterone and arginine vasopressin, possibly involving in the pathogenesis of delayed development and elevated self-grooming in male offspring. These findings hint that improving dam’s postpartum maternal behavior might be a potential regime to counteract delayed development and elevated self-grooming in male MIA offspring.

Slope reinforcement is a common method to solve the problem of slope instability, and reasonable optimization of the corresponding support parameters is crucial for practical engineering. In this paper, the slope support method of Manyanpo tunnel entrance section is taken as an example, and the theoretical calculation method is used to optimize the project cost. Combined with the orthogonal test, the sensitivity analysis of the influencing factors of the stability of the support system and the selection of the optimal parameter combination scheme are carried out. Then, based on flac3d software, the optimization scheme is compared with the original design scheme. The results show that the safety factor of the optimized scheme is increased from 1.32 to 1.43 compared with the actual project. The optimized support parameters have better control effect on the displacement of the slope, especially in the Z direction. The optimized parameters have better support effect. This study can provide reference for the optimization design of slope engineering support.

Since implementing the postdoctoral system in China, the number and quality of postdocs have improved greatly. Under the policy of creating world-class universities, most universities have focused unprecedentedly on recruiting postdoctoral fellows, and the management regulations for postdocs have become increasingly diverse. Through in-depth interviews with postdoctoral fellows at three universities in a metropolitan city, we found that postdoctoral roles have been multidimensional and sometimes conflicting, including the quasi-role of university teacher, the rigid role of independent researcher, the inertial role of student and the unofficial role of associate supervisor. Sociocultural norms, institutional contexts, and professional community shape these role identities.

Background An older age contributes to the development of bladder cancer. However, the relationship between advanced age at the diagnosis and prognosis of bladder cancer has been few reported. This study aimed to determine the effect of age on survival in bladder cancer with different subgroups. Methods 117,275 patients with bladder cancer, identified from the Surveillance, Epidemiology, and End Results database during 2004-2015 in America, were divided into 4 age groups (≤54, 55 to 64, 65 to 74, and ≥75 years). Multivariable Cox proportional-hazards model and competing risk model were conducted according to different age groups. Heat maps were plotted to show the impact of age on survival in subgroups classified by other clinicopathological variables. Moreover, restricted cubic spline was used to model the association between age and the risk of death. Results Patients aged ≥75 years had shorter overall survival in comparison with those aged ≤54 years (hazard ratio [HR] = 5.36, 95% confidence interval [CI] = 5.13-5.59). Compared with patients aged ≤54 years, patients older than 75 years experienced a decreased rate of bladder cancer-specific survival (subdistribution HR = 2.15, 95% CI = 2.04-2.25). Heat maps also showed that older ages were associated with worse overall cumulative mortality and bladder cancer-specific cumulative mortality. Similarly, restricted cubic spline verified the impact of age on survival of bladder cancer. Conclusions Age at diagnosis of bladder cancer was found to be a significant predictor for the worse overall survival and bladder cancer-specific survival even in an era with more effective therapies. Exploring the reasons why older age contributes to poor outcomes for bladder cancer will be the focus of future research.

Tibetan pigs, an indigenous pig breed in China, have high overall fat deposition and flavorful and tasty meat. They are thus good models for studying adipogenesis. Few studies have been conducted focusing on expression of lipid regulated genes in different adipose tissues of Tibetan pigs. Therefore, we compared the difference of histomorphology and expression level of lipid regulated genes through qPCR and western blot in subcutaneous fat, perirenal fat, omental adipose tissue, and inguinal fat of Tibetan pigs. Our results showed that the area of subcutaneous adipocytes in Tibetan pigs was smaller, while the other three adipose tissues (perirenal fat, greater omentum fat, inguinal fat) had cell areas of similar size. The gene expression of FABP4, FASN, FABP3, and ME1 in subcutaneous fat was significantly higher than that in perirenal fat. Furthermore, the protein expression of FABP4 was significantly lower in subcutaneous fat than in perirenal fat (p < 0.05), and the expression of FASN was higher in greater omentum fat than in subcutaneous fat (p = 0.084). The difference in adipocyte cell size and expression of lipid-regulated genes in adipose tissues from the various parts of the pig body is likely due to the different cellular lipid metabolic processes. Specially, FABP4 and FASN may be involved in the regulation of fat deposition in different adipose tissues of Tibetan pigs.

Mucopolysaccharidosis (MPS) is a progressive genetic disease that causes a deficiency in lysosomal enzymes, which play an important role in the degradation pathway of glycosaminoglycans. As a result of enzyme defects, mucopolysaccharides cannot be metabolized and thus accumulate. The cervical spine is one of the most commonly involved sites; thus, prompt surgical management before the onset of severe neurological deterioration is critical. However, because of the rarity of the disease, there is no standard treatment. In this review, we characterize the cervical spinal involvement in pediatric patients with MPS, describe the useful imaging technologies for diagnosis, and provide screening procedure for children with MPS. Surgical managements, including indications, surgical methods, possible difficulties, and solutions, are reviewed in detail.

Triple-negative breast cancer (TNBC) is an aggressive subset of breast cancer and currently lacks effective therapeutic targets. As two main phototherapeutic methods, photothermal therapy (PTT) and photodynamic therapy (PDT) show many advantages in TNBC treatment, and their combination with chemotherapy can achieve synergistic therapeutic effects. In the present study, a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane (LPHM) and dendritic large pore mesoporous silicon nanoparticles (DLMSNs). A near infrared (NIR) fluorescent dye IR780 and a chemotherapeutic drug doxorubicin (DOX) were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780 (DDI) nanoparticles (NPs), followed by camouflage with LPHM to obtain LPHM@DDI NPs. Through the mediation of LPHM, LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo. Upon NIR laser irradiation, LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells, and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis. These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy. Altogether, this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.

Abstract Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular carcinoma is largely unknown. CircRNA microarray was performed to identify abnormally expressed circRNAs in HCC tissue samples. We conducted Kaplan–Meier survival analysis to explore the significance of circUBE2J2 in clinical prognosis. Then, we examined the functions of circUBE2J2 in HCC by cell proliferation, migration, and mouse xenograft assay. We identified miR-370-5P as a circUBE2J2-related microRNA by using biotin-labeled circUBE2J2 probe to perform RNA antisense purification (RAP) assay in HCC cells. The dual luciferase reporter assay and RNA pulldown assays were employed to verify the relationships among circUBE2J2, miRNA-370-5P, and KLF7. Microarray analysis and qRT-PCR verified a circRNA termed circUBE2J2 that was downregulated in HCC. Kaplan–Meier survival analysis showed that downregulated circUBE2J2 was correlated with poorer survival. CircUBE2J2 expression in HCC cells was selectively regulated via luciferase reporter assays; circUBE2J2 and KLF7 were observed to directly bind to miR-370-5P. Furthermore, knockdown of circUBE2J2 in HCC could downregulate KLF7, the target of miR-370-5P, thus promoting the proliferation and migration of HCC cells. Then the related experiment suggested that circUBE2J2 could regulate the expression of KLF7 by sponging miR-370-5p. In summary, we infer that circUBE2J2 may act as a competing endogenous RNA (ceRNA) to regulate KLF7 expression through sponging miR-370-5P and play a regulatory functions in HCC. CircUBE2J2 may be a diagnostic biomarker and potential target for HCC therapy.

Background:. Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation. Methods:. BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay. Results:. In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P

Abstract Background Paraneoplastic neurological syndromes (PNSs) are broad-spectrum disorders that can affect any part of the nervous system varying in core symptoms. Onconeural antibodies, including Hu, Yo, Ri, anti-CV2, amphiphysin, Ma2, and Tr are well-characterized and commonly used for the diagnosis of definite PNS. Generally, anti-CV2 antibodies have usually been associated with cerebellar ataxia, chorea, peripheral and autonomic neuropathies, myelopathy, optic neuritis, and retinitis. However, Parkinsonism has not been reported as the core symptom in patients with anti-CV2 antibodies. Case presentation We report a patient with anti-CV2 antibody manifested as Parkinsonism and autonomic dysfunction, which may lead to the diagnosis of multiple system atrophy with predominant Parkinsonism (MSA-P). A lumbar puncture examination was undergone to find a positive anti-CV2 antibody in cerebrospinal fluid. PET-CT showed no tumor. Immunotherapy was adopted and the symptoms were relieved for 5 months. However, with no evidence of tumor, he died after 8 months. Conclusions Our findings indicate that PNS with anti-CV2 antibody can be shown as MSA-P mimic. Considering that MSA is a neurodegenerative disease with a poor prognosis, screening for other treatable or controllable factors like PNS presented in this case is necessary when encountering a rapid progressive MSA-mimic patient.

Objective: To investigate clinical application of aconite root (Aconitum carmichaelii Debx.; hereinafter “aconite”) by traditional Chinese medicine (TCM) physicians in TCM hospitals in Beijing and explore the specific use of aconite and the effect of different doses on decoction time. Methods: This was a cross-sectional study using two-stage sampling. Questionnaires were administered among TCM physicians from TCM hospitals in Beijing between September 2020 and August 2021. The questionnaire mainly included general demographics, clinical backgrounds of TCM physicians, and clinical application of aconite. The data analyses were performed using SPSS 20.0. Results: A total of 387 questionnaires were collected, of which 385 were valid. Of the 385 participating TCM physicians, 331 (85.97%) used aconite in clinical practice. The top three medical diagnoses treated with aconite were heart failure, diarrhea without cause, and chronic gastritis. The TCM pattern treated most frequently with a high dose of aconite was spleen-kidney yang deficiency, and the TCM pattern treated most frequently with a low dose was spleen yang deficiency, while spleen-kidney yang deficiency was treated most frequently with a common dose of aconite. The top three common formulas were Sini decoction, Mahuang Xixin Fuzi decoction, and Zhenwu decoction. Hei Shun Pian was the most common herbal pieces of aconite. The highest frequency of the maximum dose of aconite was 15 g, that of the minimum dose was 3 g, and that of the common dose was 10 g. There was a certain correlation between decoction time and the dose of aconite. Most TCM physicians advised their patients to take medicine twice a day. Conclusion: In this study, we refined and quantified the use of aconite and enriched the exploration of the clinical application of aconite besides its provisions in the Pharmacopoeia of the People's Republic of China.

Herbivore-induced defense responses are often specific, whereas plants could induce distinct defense responses corresponding to infestation by different herbivorous insects. Brown plant hopper (BPH) Nilaparvata lugens, a phloem-feeding insect, and rice leaf folder (LF) Cnaphalocrocis medinalis, a chewing insect, are both specialist herbivores on rice. To characterize the distinct resistance primed by prior damage to these two specialist herbivores, we challenged rice plants with two herbivores during vegetative growth of parent plants and assessed plant resistance in subsequent ratoons. Here, we show that LF and BPH induce different suites of defense responses in parent rice plants, LF induced higher level of JA accumulation and OsAOS, OsCOI1 transcripts, while BPH induced higher accumulation of SA and OsPAL1 transcripts. Moreover, an apparent loss of LF resistance was observed in OsAOS, OsCOI1 RNAi lines. Ratoon plants generated from parents receiving prior LF infestation exhibited higher jasmonic acid (JA) levels and elevated levels of transcripts of defense-related genes associated with JA signaling, while ratoon generated from parents receiving prior BPH infestation exhibited higher salicylic acid (SA) levels and elevated levels of transcripts of defense-related genes associated with SA signaling. Moreover, previous LF infestation obviously elevated ratoons resistance to LF, while previous infestation by BPH led to enhanced resistance in ratoons to BPH. Pre-priming of ratoons defense to LF was significantly reduced in OsAOS and OsCOI1 RNAi plant, but silencing OsAOS and OsCOI1 did not attenuate ratoons resistance to BPH. These results suggest that infestation of two specialist herbivores with different feeding styles in parent crop led to distinct defense responses in subsequent rations, and the acquired resistance to LF in ratoons is associated with priming of jasmonic acid-dependent defense responses.

Transmission of bacterial endospores between the environment and people and the following germination in vivo play critical roles in both the deadly infections of some bacterial pathogens and the stabilization of the commensal microbiotas in humans. Our knowledge about the germination process of different bacteria in the mammalian gut, however, is still very limited due to the lack of suitable tools to visually monitor this process. We proposed a two-step labeling strategy that can image and quantify the endospores’ germination in the recipient’s intestines. Endospores collected from donor’s gut microbiota were first labeled with fluorescein isothiocyanate and transplanted to mice via gavage. The recipient mice were then administered with Cyanine5-tagged D-amino acid to label all the viable bacteria, including the germinated endospores, in their intestines in situ. The germinated donor endospores could be distinguished by presenting two types of fluorescent signals simultaneously. The integrative use of cell-sorting, 16S rDNA sequencing, and fluorescence in situ hybridization (FISH) staining of the two-colored bacteria unveiled the taxonomic information of the donor endospores that germinated in the recipient’s gut. Using this strategy, we investigated effects of different germinants and pre-treatment interventions on their germination, and found that germination of different commensal bacterial genera was distinctly affected by various types of germinants. This two-color labeling strategy shows its potential as a versatile tool for visually monitoring endospore germination in the hosts and screening for new interventions to improve endospore-based therapeutics.

BackgroundRegulatory T cells (Tregs) have been found to play crucial roles in immune tolerance. However, the status of Tregs in refractory rheumatoid arthritis (RA) is still unclear. Moreover, low-dose interleukin-2 (IL-2) has been reported to selectively promote the expansion of Tregs. This study investigated the status of CD4+ Tregs and low-dose IL-2 therapy in patients with refractory RA.MethodsThe absolute number of CD4+CD25+FOXP3+ Treg (CD4 Treg), CD4+IL17+ T (Th17), and other subsets in peripheral blood (PB) from 41 patients with refractory RA and 40 healthy donors was characterized by flow cytometry combined with an internal microsphere counting standard. Twenty-six patients with refractory RA were treated with daily subcutaneous injections of 0.5 million IU of human IL-2 for five consecutive days. Then, its effects on CD4 Treg and Th17 cells in PB were analyzed.ResultsA decrease in the absolute number of PB CD4 Tregs rather than the increase in the number of Th17 was found to contribute to an imbalance between Th17 and CD4 Tregs in these patients, suggesting an essential role of CD4 Tregs in sustained high disease activity. Low-dose IL-2 selectively increased the number of CD4 Tregs and rebalanced the ratio of Th17 and CD4 Tregs, leading to increased clinical symptom remission without the observed side effects.ConclusionsAn absolute decrease of PB CD4 Tregs in patients with refractory RA was associated with continuing disease activation but not the increase of Th17 cells. Low-dose IL-2, a potential therapeutic candidate, restored decreased CD4 Tregs and promoted the rapid remission of patients with refractory RA without overtreatment and the observed side effects.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=13909, identifier ChiCTR-INR-16009546.

BackgroundPrimary healthcare professionals were overworked and psychologically overwhelmed during the COVID-19 pandemic. Resilience is an important shield for individuals to cope with psychological stress and improve performance in crises. This study aims to explore the association of individual resilience with organizational resilience, perceived social support and job performance among healthcare professionals in township health centers of China during the COVID-19 pandemic.MethodsData from 1,266 questionnaires were collected through a cross-sectional survey conducted in December 2021 in Shandong Province, China. Descriptive analysis of individual resilience, organizational resilience, perceived social support, and job performance was conducted. Pearson correlation analysis was used to examine the correlations among these variables, and structural equation modeling was performed to verify the relationships between these variables.ResultsThe score of individual resilience was 101.67 ± 14.29, ranging from 24 to 120. Organizational resilience (β = 0.409, p

Summary: Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or TBK1 alleviates podocyte injury and improves renal functions in cultured podocytes or mouse models of diabetes and obesity. These results suggest that the mtDNA-cGAS-STING pathway promotes podocyte injury and is a potential therapeutic target for DKD or other obesity-related kidney diseases.

The glioma tumor microenvironment plays a crucial role in the development, occurrence, and treatment of gliomas. Glioma-associated macrophages (GAMs) are the most widely infiltrated immune cells in the tumor microenvironment (TME) and one of the major cell populations that exert immune functions. GAMs typically originate from two cell types-brain-resident microglia (BRM) and bone marrow-derived monocytes (BMDM), depending on a variety of cytokines for recruitment and activation. GAMs mainly contain two functionally and morphologically distinct activation types- classically activated M1 macrophages (antitumor/immunostimulatory) and alternatively activated M2 macrophages (protumor/immunosuppressive). GAMs have been shown to affect multiple biological functions of gliomas, including promoting tumor growth and invasion, angiogenesis, energy metabolism, and treatment resistance. Both M1 and M2 macrophages are highly plastic and can polarize or interconvert under various malignant conditions. As the relationship between GAMs and gliomas has become more apparent, GAMs have long been one of the promising targets for glioma therapy, and many studies have demonstrated the therapeutic potential of this target. Here, we review the origin and activation of GAMs in gliomas, how they regulate tumor development and response to therapies, and current glioma therapeutic strategies targeting GAMs.

The G-protein-coupled receptor GPR84, activated by medium-chain fatty acids, primarily expressed in macrophages and microglia, is involved in inflammatory responses and retinal development in mammals and amphibians. However, our understanding of its structure, function, tissue expression, and signaling pathways in fish is limited. In this study, we cloned and characterized the coding sequence of GPR84 (ciGPR84) in grass carp. A phylogenetic analysis revealed its close relationship with bony fishes. High expression levels of GPR84 were observed in the liver and spleen. The transfection of HEK293T cells with ciGPR84 demonstrated its responsiveness to medium-chain fatty acids and diindolylmethane (DIM). Capric acid, undecanoic acid, and lauric acid activated ERK and inhibited cAMP signaling. Lauric acid showed the highest efficiency in activating the ERK pathway, while capric acid was the most effective in inhibiting cAMP signaling. Notably, DIM did not activate GPR84 in grass carp, unlike in mammals. These findings provide valuable insights for mitigating chronic inflammation in grass carp farming and warrant further exploration of the role of medium-chain fatty acids in inflammation regulation in this species.

Polyphenols are important functional substances produced in the acetic acid fermentation (AAF) of Shanxi aged vinegar (SAV). Previous studies have shown that the metabolic activity of microorganisms is closely related to polyphenol production and accumulation. In this study, microorganisms in the AAF of SAV were analyzed to explore how to increase the polyphenol yield by changing the microorganisms and reveal the potential mechanism of the microbial influence on the polyphenol yield. Macrotranscriptome analysis showed that acetic and lactic acid bacteria dominated the AAF fermentation process and initially increased and decreased. Spearman correlation analysis and verification experiments showed that the co-addition of Acetobacter pasteurianus and Lactobacillus helveticus promoted the accumulation of polyphenols, and the total polyphenol content increased by 72% after strengthening.

BACKGROUND Tungsten molybdenum ores are strategic mineral resources. China is a large producer and consumer of tungsten and molybdenum ore. Accurate and efficient analysis of tungsten and molybdenum and its associated beneficial and harmful elements is of great significance for the evaluation and comprehensive utilization of tungsten and molybdenum ore deposits. Acid dissolution and alkali fusion are the general digestion methods in tungsten molybdenum ore analysis. However, the acid solution method cannot be used to overcome the hydrolysis problem when treating samples with high content of tungsten and molybdenum, whereas the alkali fusion method such as sodium peroxide and sodium hydroxide usually introduces a large content of alkali metals, so the determination of potassium and sodium cannot be finished. OBJECTIVES To find an efficient method for the determination of tungsten, molybdenum and 11 other elements in tungsten molybdenum ore. METHODS Lithium metaborate melting-tartaric acid ultrasonic leaching and inductively coupled plasma-optical emission spectrometry (ICP-OES) was used for the simultaneous determination of tungsten, molybdenum, copper, lead, zinc, aluminum, iron, calcium, magnesium, titanium, manganese, potassium and sodium in tungsten-molybdenum ore. The sample was completely digested by lithium metaborate fusion. No other elements were introduced except for B and Li. Tartaric acid was used to inhibit the hydrolysis of tungsten and molybdenum. Ultrasonic leaching speeds up the dissolution of the frit. RESULTS The experiment optimized the analysis spectrum and observation method of each element, compared the amount of flux and instrument conditions to obtain the best conditions, and used the matrix matching method to draw a standard curve to eliminate the influence of the matrix effect. The linear correlation coefficient of the standard curve of each element was greater than 0.9990, the detection limit of the method was 1.34-46.2μg/g, the relative error of measured results was 0.14%-8.7%, the relative standard deviation (RSD, n=10) of the measured results was 1.4%-7.6%. CONCLUSIONS This method can accurately and efficiently complete the simultaneous determination of multiple elements in tungsten and molybdenum ore samples.

BACKGROUND Sepiolite is a very important non-metallic mineral, which is widely used in aviation, animal husbandry, the chemical industry, environmental protection and other fields. Sepiolite is in great demand and needs a lot of analysis and testing. However, the existing sepiolite reference materials are inadequate and do not satisfy the needs of sepiolite composition analysis. Furthermore, there are no sepiolite reference materials in China, making it necessary to develop one. OBJECTIVES To prepare a reference material for composition analysis of sepiolite whose certified value components cover as many elements as possible. METHODS Sepiolite samples were collected from Xiangtan, Hunan Province. The samples were subjected to primary crushing, coarse-grain sieving, inactivation, fine grinding and fine grain sieving. After passing the initial inspection, samples were bottled and numbered. Random samples were taken for homogeneity test, stability test. 24 components were selected for homogeneity and stability test. RESULTS The results showed that the RSD of 20 components were less than 3%, and the F value of the variance test was less than the critical value of the list[F0.05(29, 60)=1.65], indicating that the homogeneity of the reference material was good. During the investigation period, the contents of 24 components had no significant change, indicating that the standard material was stable. Nine laboratories cooperated with traditional chemical analysis methods and modern instrumental analysis methods to determine the value. The final values were 63 components, covering major, trace and all rare earth elements. The contents of characteristic components MgO and LOI were 18% and 8.55%, respectively. These two components form a certain ladder with the existing reference materials, which can better satisfy the requirements of sepiolite composition analysis. CONCLUSIONS The developed sepiolite reference material can be used as the quality control standards for geological prospecting, geochemical investigation and testing of geological and mineral products, as well as for other industries to analyze similar materials. Moreover, in the process of developing the reference material, improvements and developments to the new methods will provide technical support for the subsequent development of the sepiolite reference material.

Objective: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease. However, the mechanism of C3a/C4a in osteoclasts MM patients remains unclear. Methods: The formation and function of osteoclasts were analyzed after adding C3a/C4a in vitro. RNA-seq analysis was used to screen the potential pathways affecting osteoclasts, and the results were verified by Western blot, qRT-PCR, and pathway inhibitors. Results: The osteoclast area per view induced by 1 μg/mL (mean ± SD: 50.828 ± 12.984%) and 10 μg/mL (53.663 ± 12.685%) of C3a was significantly increased compared to the control group (0 μg/mL) (34.635 ± 8.916%) (P < 0.001 and P < 0.001, respectively). The relative mRNA expressions of genes, OSCAR/TRAP/RANKL/cathepsin K, induced by 1 μg/mL (median: 5.041, 3.726, 1.638, and 4.752, respectively) and 10 μg/mL (median: 5.140, 3.702, 2.250, and 5.172, respectively) of C3a was significantly increased compared to the control group (median: 3.137, 2.004, 0.573, and 2.257, respectively) (1 μg/mL P = 0.001, P = 0.003, P < 0.001, and P = 0.008, respectively; 10 μg/mL: P < 0.001, P = 0.019, P < 0.001, and P = 0.002, respectively). The absorption areas of the osteoclast resorption pits per view induced by 1 μg/mL (mean ± SD: 51.464 ± 11.983%) and 10 μg/mL (50.219 ± 12.067%) of C3a was also significantly increased (33.845 ± 8.331%) (P < 0.001 and P < 0.001, respectively) compared to the control. There was no difference between the C4a and control groups. RNA-seq analysis showed that C3a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase (PI3K) signaling pathway. The relative expressions of PIK3CA/phosphoinositide dependent kinase-1 (PDK1)/serum and glucocorticoid inducible protein kinases (SGK3) genes and PI3K/PDK1/p-SGK3 protein in the C3a group were significantly higher than in the control group. The activation role of C3a in osteoclasts of MM patients was reduced by the SGK inhibitor (EMD638683). Conclusions: C3a activated osteoclasts by regulating the PI3K/PDK1/SGK3 pathways in MM patients, which was reduced using a SGK inhibitor. Overall, our results identified potential therapeutic targets and strategies for MBD patients.

Abstract Background Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating type 2 diabetes mellitus (T2DM) in clinical studies. Accumulating evidence has suggested that the therapeutic effects of MSCs are not due to their direct differentiation into functional β-cells but are instead mediated by their paracrine functions. Among them, exosomes, nano-sized extracellular vesicles, are important substances that exert paracrine functions. However, the underlying mechanisms of exosomes in ameliorating T2DM remain largely unknown. Methods Bone marrow mesenchymal stem cell (bmMSC)-derived exosomes (bmMDEs) were administrated to T2DM rats and high-glucose-treated primary islets in order to detect their effects on β-cell dedifferentiation. Differential miRNAs were then screened via miRNA sequencing, and miR-146a was isolated after functional verification. TargetScan, reporter gene detection, insulin secretion assays, and qPCR validation were used to predict downstream target genes and involved signaling pathways of miR-146a. Results Our results showed that bmMDEs reversed diabetic β-cell dedifferentiation and improved β-cell insulin secretion both in vitro and in vivo. Results of miRNA sequencing in bmMDEs and subsequent functional screening demonstrated that miR-146a, a highly conserved miRNA, improved β-cell function. We further found that miR-146a directly targeted Numb, a membrane-bound protein involved in cell fate determination, leading to activation of β-catenin signaling in β-cells. Exosomes derived from miR-146a-knockdown bmMSCs lost the ability to improve β-cell function. Conclusions These findings demonstrate that bmMSC-derived exosomal miR-146a protects against diabetic β-cell dysfunction by acting on the NUMB/β-catenin signaling pathway, which may represent a novel therapeutic strategy for T2DM.

PTENα is an N-terminally extended isoform of PTEN, a gene frequently mutated in human cancers. Here the authors show that PTENα remains active in PTEN-mutant cancers and is associated with tumor immune escape by promoting tumor cell resistance to T cell cytotoxicity.

Abstract Background Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-β) signaling pathway is becoming a reality. However, the molecular characterization of TGF-β associated signatures in GIAD requires further exploration. Methods Multi-omics data were collected from TCGA and GEO database. A pivotal unsupervised clustering for TGF-β level was performed by distinguish status of TGF-β associated genes. We analyzed differential mRNAs, miRNAs, proteins gene mutations and copy number variations in both clusters for comparison. Enrichment of pathways and gene sets were identified in each type of GIAD. Then we performed differential mRNA related drug response by collecting data from GDSC. At last, a summarized deep neural network for TGF-β status and GIADs was constracted. Results The TGF-βhigh group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-βhigh group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-β. Further genomic analysis showed that TGF-βlow group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed tumor-sensitive or tumor-resistant drugs corresponding to TGF-β associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-β status in different GIAD datasets. Conclusions We provide molecular signatures associated with different levels of TGF-β to deepen the understanding of the role of TGF-β in GIAD and provide potential drug possibilities for therapeutic targets in different levels of TGF-β in GIAD.

Abstract Fluopyram is commonly used to control banana leaf spot, anthracnose, and scab in tropical agricultural areas. To explore its behaviour in tropical agricultural environments, dissipation, adsorption, and leaching behaviours of fluopyram in three typical banana planting soils were studied. Also, its dissipation and migration capabilities in different regions and different soil types were evaluated. The results showed that the dissipation of fluopyram was in accordance with the first-order kinetic equation in the three banana soils, but the degradation rates were quite different. The degradation half-lives in the Hainan latosol, Yunnan sandy soil, and Fujian Plain alluvial soil were 46.21 days, 36.48 days and 57.76 days, respectively. Fluopyram also exhibited high adsorption and low leachability in the three soils. The Fujian Plain alluvial soil had the highest adsorption capacity for fluopyram, while fluopyram had the low leachability in the Yunnan sandy soil.