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Abstract Background Gynostemma pentaphyllum, an ancient Chinese herbal medicine, serves as a natural source of gypenosides with significant medicinal properties. Basic helix-loop-helix (bHLH) transcription factors play pivotal roles in numerous biological processes, especially in the regulation of secondary metabolism in plants. However, the characteristics and functions of the bHLH genes in G. pentaphyllum remain unexplored, and their regulatory role in gypenoside biosynthesis remains poorly elucidated. Results This study identified a total of 111 bHLH members in G. pentaphyllum (GpbHLHs), categorizing them into 26 subgroups based on shared conserved motif compositions and gene structures. Collinearity analysis illustrated that segmental duplications predominately lead to the evolution of GpbHLHs, with most duplicated GpbHLH gene pairs undergoing purifying selection. Among the nine gypenoside-related GpbHLH genes, two GpbHLHs (GpbHLH15 and GpbHLH58) were selected for further investigation based on co-expression analysis and functional prediction. The expression of these two selected GpbHLHs was dramatically induced by methyl jasmonate, and their nuclear localization was confirmed. Furthermore, yeast one-hybrid and dual-luciferase assays demonstrated that GpbHLH15 and GpbHLH58 could bind to the promoters of the gypenoside biosynthesis pathway genes, such as GpFPS1, GpSS1, and GpOSC1, and activate their promoter activity to varying degrees. Conclusions In conclusion, our findings provide a detailed analysis of the bHLH family and valuable insights into the potential use of GpbHLHs to enhance the accumulation of gypenosides in G. pentaphyllum.

Abstract Purpose This study aimed to characterise the whole-genome structure of two clinical Klebsiella pneumoniae strains co-harbouring mcr-8.1 and tmexCD1-toprJ1, both resistant to colistin and tigecycline. Methods K. pneumoniae strains TGC-02 (ST656) and TGC-05 (ST273) were isolated from urine samples of different patients hospitalised at separate times in 2021. Characterisation involved antimicrobial susceptibility testing (AST), conjugation assays, whole-genome sequencing (WGS), and bioinformatics analysis. Comparative genomic analysis was conducted on mcr-8.1-carrying and tmexCD1-toprJ1-carrying plasmids. Results Both K. pneumoniae isolates displayed a multidrug-resistant phenotype, exhibiting resistance or reduced susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, aztreonam, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, apramycin, tigecycline and colistin. WGS analysis revealed that clinical strain TGC-02 carried the TmexCD1-toprJ1 gene on a 200-Kb IncFII/IncFIB-type plasmid, while mcr-8 was situated on a 146-Kb IncFII-type plasmid. In clinical strain TGC-05, TmexCD1-toprJ1 was found on a 300-Kb IncFIB/IncHI1B/IncR-type plasmid, and mcr-8 was identified on a 137-Kb IncFII/IncFIA-type plasmid. Conjugation experiments assessed the transferability of these plasmids. While transconjugants were not obtained for TGC-05 despite multiple screening with tigecycline or colistin, pTGC-02-tmex and pTGC-02-mcr8 from clinical K. pneumoniae TGC-02 demonstrated self-transferability through conjugation. Notably, the rearrangement of pTGC-02-tmex and pTGC-02-mcr8 via IS26-based homologous recombination was observed. Moreover, the conjugative and fusion plasmids of the transconjugant co-harboured the tmexCD1-toprJ1 gene cluster and mcr-8.1, potentially resulting from IS26-based homologous recombination. Conclusion The emergence of colistin- and tigecycline-resistant K. pneumoniae strains is concerning, and effective surveillance measures should be implemented to prevent further dissemination.

Abstract Background Brain magnetic resonance imaging (MRI) rarely reveals structural changes in patients with suspected anti-Tr/DNER encephalitis and thus provides very limited information. Here, we combined structural MRI, functional MRI, and positron emission tomography-computed tomography (PET-CT) findings to characterize this rare disorder in a patient. Case presentation A 43-year-old woman presented with progressive cerebellar ataxia, memory impairment, anxiety, and depression. Anti-Tr antibodies were detected in both her serum (1:10) and cerebrospinal fluid (1:10). A diagnosis of anti-Tr-positive autoimmune cerebellar ataxia was established. The patient’s symptoms were worse, but her brain MRI was normal. Meanwhile, voxel-based morphometry analysis showed bilateral reduced cerebellar volume, especially in the posterior lobe and uvula of the cerebellum and the middle of the left temporal lobe compared with 6 sex- and age-matched healthy subjects (6 females, 43 ± 2 years; p

Abstract Human herpes virus 6 (HHV-6) is a ubiquitous and most common pathogen that affects humans. Human herpes virus 6B (HHV-6B) is a wide spread human herpesvirus that infects most people when they are children, establishes latent infections in the central nervous system (CNS), especially in the hippocampus and amygdala, and induces neurologic diseases. HHV-6 can establish a latent infection and be reactivated by various stimuli. Recently, viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients, suggesting the involvement of HHV-6B in the pathogenesis of epilepsy. Temporal lobe epilepsy (TLE) has been shown to be closely related with HHV-6B. TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis. However, the mechanisms underlying the contribution of this virus to the development of TLE remains unknown. The direct damage and immune activation caused by the virus are involved in the process of neuron damage, abnormal neural circuit formation and glial cell proliferation. In addition, some cytokines like interleukin-17A (IL-17A), nuclear factor-kappa B (NF-κb), transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK) and phospholipase A2 are up-regulated and involved in the pathological process of TLE. More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy, and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.

Abstract Objectives This study aimed to assess the health utility of leukemia patients in China using the EQ-5D-5L, compare it with the population norms, and identify the potential factors associated with health utility. Methods A hospital based cross-sectional survey was conducted in three tertiary hospitals from July 2015 to February 2016. A total of 186 patients with leukemia completed the EQ-5D-5L and their health utility scores were calculated using the Chinese value set. EQ-5D-5L utility and dimensions scores of leukemia patients were compared with China’s population norms using Kruskal–Wallis test and chi square test. Potential factors associated with health utility were identified using Tobit regression. Results The mean EQ-5D-5L utility scores of patients with leukemia, grouped by either gender or age, were significantly lower than those of the general population (p

Abstract Background Biosurfactants, being highly biodegradable, ecofriendly and multifunctional compounds have wide applications in various industrial sectors including environmental bioremediation. Surfactin, a member of lipopeptide family, which is considered as one of the most powerful biosurfactants due to its excellent emulsifying activities as well as environmental and therapeutic applications. Therefore, the aim of this study was to investigate the newly isolated bacterial strain S2MT for production of surfactin-like biosurfactants and their potential applications for oil-contaminated soil remediation. Results In this study, the strain S2MT was isolated from lake sediment and was identified as Bacillus nealsonii based on transmitted electron microscopy (TEM) and 16S rRNA ribo-typing. The strain S2MT produced biosurfactant that reduced the surface tension (34.15 ± 0.6 mN/m) and displayed excellent emulsifying potential for kerosene (55 ± 0.3%). Additionally, the maximum biosurfactant product yield of 1300 mg/L was achieved when the composition of the culture medium was optimized through response surface methodology (RSM). Results showed that 2% glycerol and 0.1% NH4NO3 were the best carbon/nitrogen substrates for biosurfactant production. The parameters such as temperature (30 °C), pH (8), agitation (100 rpm), NH4NO3 (0.1%) and NaCl (0.5%) displayed most significant contribution towards surface tension reduction that resulted in enhanced biosurfactant yield. Moreover, the extracted biosurfactants were found to be highly stable at environmental factors such as salinity, pH and temperature variations. The biosurfactants were characterized as cyclic lipopeptides relating to surfactin-like isoforms (C13–C15) using thin-layer chromatography (TLC), Ultra high performance liquid chromatography and mass spectrometry (UHPLC-MS). The crude biosurfactant product displayed up to 43.6 ± 0.08% and 46.7 ± 0.01% remediation of heavy engine-oil contaminated soil at 10 and 40 mg/L concentrations, respectively. Conclusion Present study expands the paradigm of surfactin-like biosurfactants produced by novel isolate Bacillus nealsonii S2MT for achieving efficient and environmentally acceptable soil remediation as compared to synthetic surfactants.

Abstract Seizures are a common finding in patients with tuberculous meningitis (TBM), and associate with four times increased risk of death and neurological disability, especially in children. It has been reported that brain inflammation, diffuse neuronal injury, and reactive gliosis may all contribute to the pathogenesis of seizures in TBM. Early seizure onset may be associated with meningeal irritation and cerebral oedema; while, the late seizures are usually due to infarction, hydrocephalus, tuberculoma and paradoxical response. Moreover, recurrent uncontrolled seizures can evolve to status epileptics resulting in an increased risk of chronic epilepsy and poor prognosis. Therefore, this review aimed to assess the frequency of seizures in patients with TBM, and discuss the etiologies, mechanisms, and characteristics of seizures in TBM. Besides, we have searched the literature to identify the prognostic factors for chronic epilepsy after TBM.

Abstract Background Androgen plays a pivotal role in spermatogenesis, accompanying a question how androgen acts on germ cells in testis since germ cells lack of androgen receptors (AR). Promyelocytic leukemia zinc-finger (PLZF) is essential for maintenance of undifferentiated spermatogonia population which is terminologically called spermatogonia progenitor cells (SPCs). Aims We aim to figure out the molecular connections between androgen and fates of PLZF+ SPCs population. Method Immunohistochemistry was conducted to confirm that postnatal testicular germ cells lacked endogenous AR. Subsequently, total cells were isolated from 5 dpp (day post partum) mouse testes, and dihydrotestosterone (DHT) and/or bicalutamide treatment manifested that Plzf was indirectly regulated by androgen. Then, Sertoli cells were purified to screen downstream targets of AR using ChIP-seq, and gene silence and overexpression were used to attest these interactions in Sertoli cells or SPCs-Sertoli cells co-culture system. Finally, these connections were further verified in vivo using androgen pharmacological deprivation mouse model. Results Gata2 is identified as a target of AR, and β1-integrin is a target of Wilms’ tumor 1 (WT1) in Sertoli cells. Androgen signal negatively regulate β1-integrin on Sertoli cells via Gata2 and WT1, and β1-integrin on Sertoli cells interacts with E-cadherin on SPCs to regulate SPCs fates. Conclusion Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.

Abstract Objective This meta-analysis and systematic review were conducted to comprehensively evaluate the efficacy and safety of mesenchymal stem cells in patients with acute ischemic stroke. Method We conducted a manual search of electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, with a search deadline set for February 1, 2023. Data analysis was performed using Stata version 15.0. Result A total of 9 randomized controlled studies were included, involving a total of 316 people, including 159 mesenchymal stem cells and 147 control groups. Results of meta-analysis: Compared to a placebo group, the administration of mesenchymal stem cells resulted in a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) scores among patients diagnosed with acute ischemic stroke [SMD=-0.99,95% CI (-1.93, -0.05)]. Compared to placebo, barthel index [SMD = 0.48,95% CI (-0.55,1.51)], modified rankin score [SMD = 0.45, 95% CI (1.11, 0.21)], adverse events (RR = 0.68, 95% CI (0.40, 1.17)] the difference was not statistically significant. Conclusion Based on current studies, mesenchymal stem cell transplantation can ameliorate neurological deficits in patients with ischemic stroke to a certain extent without increasing adverse reactions. However, there was no significant effect on Barthel index and Modified Rankin score.