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Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

The mass transfer of the guest molecules in the pores is fundamental for the application of nanoporous materials like metal���organic frameworks, MOFs. In the present work, we explore the uptake and release of toluene in a series of Zr-based MOFs with different pore sizes. We find that intermolecular guest���guest interaction, sterically controlled by the pore size, has a substantial impact on the release kinetics. While the adsorption is rather fast, the desorption process is many orders of magnitude slower. Depending on the pore size, molecular clusters form, here (most likely) toluene dimers, which are rather stable and their break-up is rate-limiting during the desorption process. This results in a step-like desorption kinetics, deviating from the plain Fickian-diffusion-controlled release. Temperature-dependent experiments show that the minimum and maximum of the release rates are obtained at the same toluene loadings, independent of the temperature. Moreover, the activation energy for the release coincides with the binding energy of a toluene dimer. The work shows the importance of intermolecular guest���guest interaction, controlled by the MOF-nanoconfinement, for the uptake and release from nanoporous materials.

Electronic circular dichroism is an important optical phenomenon offering insights into chiral molecular materials. On the other hand, metal-organic frameworks (MOFs) are a novel group of crystalline porous thin-film materials that provide tailor-made chemical and physical properties by carefully selecting their building units. Combining these two aspects of contemporary material research and integrating chiral molecules into MOFs promises devices with unprecedented functionality. However, considering the nearly unlimited degrees of freedom concerning the choice of materials and the geometrical details of the possibly structured films, we urgently need to complement advanced experimental methods with equally strong modeling techniques. Most notably, these modeling techniques must cope with the challenge that the material and devices thereof cover size scales from {\AA}ngstr\"oms to mm. In response to that need, we outline a computational workflow that seamlessly combines quantum chemical methods to capture the properties of individual molecules with optical simulations to capture the properties of functional devices made from these molecular materials. We concentrate on chiral properties and apply our work to UiO-67-BINOL MOFs, for which experimental results are available to benchmark the results of our simulations and explore the optical properties of cavities and metasurfaces made from that chiral material.

The exploitation of ion-absorbed rare earth elements (REEs) has caused serious ecological destruction and environmental pollution. Effects on soil fungal structure and diversity exerted by mining activities are usually ignored, although fungus is one of the most important components in soil ecosystems. In the present research, quantitative polymerase chain reaction (qPCR) and high-throughput Illumina MiSeq sequencing were conducted to characterize fungal community composition and structure in soil of a rare earth mining area after in situ leaching. Statistical analyses, network, and FUNGuild were used to conduct in-depth analyses. Ascomycota, Basidiomycota, and Glomeromycota were the most abundant phyla in the mining soils. Fungal community structures were stable after leaching practice, but nutrition contents (organic matter, TC, and TN) significantly and positively contributed to fungal abundances and diversities. Saprotrophs in phyla Ascomycota and Basidiomycota were the dominant fungal trophic mode, and they played critical roles in nutrient cycling, transformation processes, and reducing REE toxicity. Symbiotrophs of phyla Glomeromycota contributed to soil aggregation and slowing down nutrient losses after in situ leaching practice. In addition, fungi could regulate the interactions between species to resist the harsh environment of REE toxicity or ammonium caused by in situ leaching practice.

[Image: see text] The selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-d]pyrimidine scaffold. The optimization of this pyrrolo[2,3-d]pyrimidine core resulted in compound 1, which demonstrated potent in vitro RET kinase inhibition and robust in vivo efficacy in RET-driven tumor xenografts upon multiday dosing in mice. The administration of 1 was well-tolerated at established efficacious doses (10 and 30 mg/kg, po, qd), and plasma exposure levels indicated a minimal risk of KDR or hERG inhibition in vivo, as evaluated by Miles assay and free plasma concentrations, respectively.

Acaulospora fanjing is here described as a new species of arbuscular mycorrhizal fungi (AMF; Glomeromycota) based on morphological and phylogenetic analyses. It was associated with roots of Acer flabellatum colonizing of the massy dwarf forest to fanjing Mountain, China, and this is the only site of its occurrence known to date. A.fanjing is characterized by forming reddish orange to reddish brown globose spores of (109–)123(–138) µm diam and three layers of outer spore walls (SWL1–SWL3) and two layers of germinal walls (MW and IW). SWL1 hyaline, short–lived, evanescent, SWL2 laminate, orange to reddish orange, 2.0–3.5 μm thick and SWL3 thin, difficult to observe; MW is hyaline, bilayered (MWL1–MWL2), semiflexible; IW is hyaline, with three layers and not “beaded” structure, only the IWL2 were stained light pink in Melzer’s reagent. A.fanjing can be distinguished from all other Acaulospora species by spore size, color and spore wall structure. Phylogenetic analysis based on the AMF extended DNA barcode covering a 1.5-kb fragment of the small subunit (SSU), internal transcribed spacer region (ITS), and the large subunit (LSU) of rRNA genes places A.fanjing in the genus Acaulospora, separated from other described Acaulospora species. All available sequences in public databases suggest that this new fungal species has not yet been previously detected.

Advanced breast cancer (BC), especially basal like triple-negative BC (TNBC), is a highly malignant tumor without viable treatment option, highlighting the urgent need to seek novel therapeutic targets. Arylsulfatase D (ARSD), localized at Xp22.3, is a female-biased gene due to its escaping from X chromosome inactivation (XCI). Unfortunately, no systematic investigation of ARSD on BC has been reported. In this study, we observed that ARSD expression was positively related to ERα status either in BC cells or tissue specimens, which were associated with good prognosis. Furthermore, we found a set of hormone-responsive lineage-specific transcription factors, FOXA1, GATA3, ERα, directly drove high expression of ARSD through chromatin looping in luminal subtype BC cells. Opposingly, ARSD still subjected to XCI in TNBC cells mediated by Xist, CpG islands methylation, and inhibitory histone modification. Unexpectedly, we also found that ectopic ARSD overexpression could inhibit proliferation and migration of TNBC cells by activating Hippo/YAP pathway, indicating that ARSD may be a molecule brake on ERα signaling pathway, which restricted ERα to be an uncontrolled active status. Combined with other peoples’ researches that Hippo signaling maintained ER expression and ER + BC growth, we believed that there should exist a regulative feedback loop formation among ERα, ARSD, and Hippo/YAP pathway. Collectively, our findings will help filling the knowledge gap about the influence of ARSD on BC and providing evidence that ARSD may serve as a potential marker to predict prognosis and as a therapeutic target.

In response to brain injury, resident astrocytes become reactive and play dynamic roles in neural repair and regeneration. The signaling pathways underlying such reactive astrogliosis remain largely unclear. We here show that NEK6, a NIMA-related serine/threonine protein kinase, is rapidly induced following pathological stimulations and plays critical roles in reactive astrogliosis. Enhanced NEK6 expression promotes reactive astrogliosis and exacerbates brain lesions; and conversely, NEK6 downregulation dampens injury-induced astrocyte reactivity and reduces lesion size. Mechanistically, NEK6 associates with and phosphorylates STAT3. Kinase activity of NEK6 is required for induction of GFAP and PCNA, markers of reactive astrogliosis. Interestingly, NEK6 is also localized in the nucleus and binds to STAT3-responsive genomic elements in astrocytes. These results indicate that NEK6 constitutes a molecular target for the regulation of reactive astrogliosis.

To explore a new underlying molecular mechanism of Huangkui Extract Powder (HKEP) in the alleviation of diabetic nephropathy (DN). Murine immortalized podocytes were divided into (i) normal glucose (NG, 5.6 mM), (ii) NG + HKEP (0.45 g/L), (iii) HG, and (iv) HG + HKEP (0.45 g/L) groups. MTT assay and flow cytometry were used to detect the podocyte proliferation, apoptosis and cell cycle. Cell viability was inhibited, and apoptosis increased in (iii) HG group compared with (i) NG group (p

Glycyrrhizin (GL) and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide (GAMG) are the typical triterpenoid glycosides found in the root of licorice, a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations. However, only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far. In mammals, glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases. In this study, we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate, glycyrrhetinic acid (GA) for its glycodiversification. Out of 22 selected glycosyltransferases, only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG. Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels (P82~R85) and substrates. Furthermore, the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time, resulting in the production of 5.98 ± 0.47 mg/L and 2.31 ± 0.21 mg/L of GL and GAMG, respectively.

The natural flavonoids in foods of plant origin have been well-characterized due to their beneficial biological properties. However, the information regarding the flavonoid compounds in edible insects remains severely limited. In the present study, we used a metabolomics approach to identify the flavonoid compounds in the Chinese oak silkworm, Antheraea pernyi Guerin-Meneville (Lepidoptera: Saturniidae), an traditional edible insect. Our study identified over 200 flavonoid metabolites in the larval midgut of A. pernyi with LC-ESI-MS/MS system. These flavonoid metabolites come from eight subclasses, including flavones (1 0 3), flavonols (34), flavonoids (28), flavanones (20), polyphenols (19), isoflavones (9), anthocyanins (9), and proanthocyanidins (4). The relative content of the flavones is the most abundant, with a value of 36.74% of the total. The top five flavonoid components in A. pernyi are hyperoside, isoquercitroside, tricin 7-O-hexoside, hesperetin 5-O-glucoside and protocatechuic acid, accounting for 51.17% of the total flavonoids. Hyperoside is the most abundant flavonoid compound (18.07% of the total) in A. pernyi. Our findings indicated targeted metabolomics is a useful approach to identify flavonoids in edible insects which contain abundant flavonoids than we already knew.

The hepatitis C virus (HCV), an obligatory intracellular pathogen, highly depends on its host cells to propagate successfully. The HCV life cycle can be simply divided into several stages including viral entry, protein translation, RNA replication, viral assembly and release. Hundreds of cellular factors involved in the HCV life cycle have been identified over more than thirty years of research. Characterization of these cellular factors has provided extensive insight into HCV replication strategies. Some of these cellular factors are targets for anti-HCV therapies. In this review, we summarize the well-characterized and recently identified cellular factors functioning at each stage of the HCV life cycle.

In this study, the impacts of transglutaminase (TGase)-induced glycosylation and limited enzymatic hydrolysis on the foaming property of soy protein isolates (SPI) and the possible underlying mechanisms were investigated. SPI were first glycosylated with oligochitosan by TGase to produce glycosylated samples (GSPI). GSPI were further hydrolyzed using Protamex with controlled degree of hydrolysis (DH of 1%, 2% and 4%). As compared to native SPI, the foaming stability of GSPI sample was increased from 24.3% ± 3.1% to 40.4% ± 7.6%, and the hydrolyzed GSPI showed enhanced foaming property. GSPI-1% DH showed the best foaming capacity and foam stability, increasing about 2.12 folds and 2.33 folds, respectively. Hydrodynamic-size of dominant distribution peak in GSPI and its hydrolysates (1% DH) were about 3090 and 531 nm, respectively, which were bigger than that of SPI (about 220 nm). The presence of oligochitosan in GSPI decreased surface hydrophobicity, and the subsequent hydrolysis generated an opposite effect. GSPI and its hydrolysates had more flexible tertiary conformations as revealed by intrinsic fluorescence study. Overall, high values of negative zeta potential and apparent viscosity of samples might be responsible for the improved foaming property. This study suggested that TGase-induced glycosylation and limited enzymatic hydrolysis are promising techniques for enhancing the foaming property of SPI, which would broaden the applications of SPI in food industry.

Sesquiterpenes are a large variety of terpene natural products, widely existing in plants, fungi, marine organisms, insects, and microbes. Value-added sesquiterpenes are extensively used in industries such as: food, drugs, fragrances, and fuels. With an increase in market demands and the price of sesquiterpenes, the biosynthesis of sesquiterpenes by microbial fermentation methods from renewable feedstocks is acquiring increasing attention. Synthetic biology provides robust tools of sesquiterpene production in microorganisms. This review presents a summary of metabolic engineering strategies on the hosts and pathway engineering for sesquiterpene production. Advances in synthetic biology provide new strategies on the creation of desired hosts for sesquiterpene production. Especially, metabolic engineering strategies for the production of sesquiterpenes such as: amorphadiene, farnesene, bisabolene, and caryophyllene are emphasized in: Escherichia coli, Saccharomyces cerevisiae, and other microorganisms. Challenges and future perspectives of the bioprocess for translating sesquiterpene production into practical industrial work are also discussed.

Objectives Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (MTB), has similar clinical, radiological, and histopathological characteristics to sarcoidosis (SA). Accurately distinguishing SA from TB remains a clinical challenge. Methods A total of 44 TB patients and 47 SA patients who were clinically diagnosed using chest radiography, pathological examination, routine smear microscopy, and microbial culture were enrolled in this study. The MTB genome was captured and sequenced directly from tissue specimens obtained upon operation or biopsy, and the feasibility of next-generation sequencing (NGS) for the MTB genome in the differential diagnosis of TB from SA was evaluated. Results Using a depth >10× and coverage >15% of the sequencing data, TB patients were identified via the NGS approach directly using operation or biopsy specimens without clinical pretreatment. The sensitivity, specificity, and concordance of the NGS method were 81.8% (36/44), 95.7% (45/47), and 89.0% (81/91), respectively (kappa = 0.78, 95% confidence interval 0.65–0.91; P Conclusions This study established an improved NGS strategy for rapidly distinguishing patients with TB from those with SA and has potential clinical benefits.

The development of mixed microbial agents can reduce the use of pesticides and fertilizers in agriculture. However, most previous studies focused only on the overall effects of mixed microbial agents and ignored the interactions between bacteria in mixed systems. In this study, Bacillus subtilis SL-44 and Enterobacter cloacae Rs-2 were used to explore the interactions between two different functional plant growth-promoting rhizobacteria (PGPR). The plant growth-promotion properties and inhibition rate of Rhizoctonia solani were determined, and the mechanism of the interactions under single and co-culture conditions was elucidated via transcriptomics analysis under single and co-culture conditions. Results showed that the co-culture was not conducive to B. subtilis SL-44 growth. Furthermore, the differentially expressed genes related to B. subtilis SL-44 developmental process and cell differentiation were downregulated by 82.7% and 84.8% respectively. Moreover, among the properties, only siderophore production by the mixed culture was higher than that of single cultures because of the upregulation of the siderophore-related genes of B. subtilis SL-44. In addition, results revealed the altruistic relationship between the two strains, and the chemical and non-chemical signals of their interaction. This study provides unique insights into PGPR interactions and offers guidance for the development and application of mixed microbial agents.

High temperature (HT) severely limits rice production, but effective measures can reduce the adverse effects of HT. A 2-year experiment was conducted involving five sowing dates to investigate the effects of potassium dihydrogen phosphate (KH2PO4), salicylic acid (SA), and the sowing date on the physiological characteristics, yield and quality of rice subjected to HT. Under ambient HT conditions (daily average temperature ≥ 30 °C for ≥ 3 days or maximum temperature ≥ 35 °C for ≥ 3 days), KH2PO4 (KP1-KP2: 22.05 and 36.75 mmol L−1), SA (SA1-SA2: 0.5 and 1.5 mmol L−1), and their combinations were applied to leaves from the late-booting stage to the flowering stage, with deionized water as a control (CK). Compared with CK, KP1, KP2, SA1, KP1 + SA1, and KP2 + SA1 alleviated the adverse effects of HT on the number of grains per panicle, seed set, and yield, among which SA1, KP2 + SA1, and KP1 were the best. The antioxidant enzyme (superoxide dismutase, peroxidase, and catalase) activities, levels of osmotic protective substances (soluble sugars, soluble proteins, and proline), and chlorophyll content were increased and the malonaldehyde content and leaf temperature were decreased in the SA1, KP2 + SA1, and KP1 treatments. Compared with those sown on April 25 and May 5, plants sown on May 15, May 25, and June 5 had suitable temperature conditions and presented increased grain yield and quality. Therefore, the application of SA1, KP2 + SA1, and KP1 and the use of an optimal sowing date (from May 15 to June 5) increased the rice yield and quality under HT.

Rare earth oxides doped hafnia ceramics, with a formula of Hf0.76LnxY0.24-xO1.88 (Ln = Gd, Yb, Gd + Yb or La + Yb), were prepared by solid state sintering at 1500 °C. The effects of the rare earth oxides on the microstructures, sintering resistance, and thermo-physical properties of the doped hafnia ceramics were investigated. Results show that the Gd-Y, Yb-Y or Gd-Yb-Y co-doped hafnia ceramics remain the same defect fluorite (F) structure, while the La-Yb-Y co-doped hafnia revealing coexistence of pyrochlore (P) and fluorite structures. Yb-Y co-doped samples exhibited much better sintering resistance compared with Gd-Y and Gd-Yb-Y co-doped samples. The coexistence of P and F phases is beneficial to improved sintering capability. The thermal conductivities of the Gd-Y, Yb-Y and Gd-Yb-Y doped samples are relatively lower (1.4-1.7 W m−1 K−1 at 1200 °C), but for the La-Yb-Y co-doped samples, the thermal conductivity increases dramatically with temperature due to increased thermal radiation at high-temperature. The average thermal expansion coefficients (TECs) of the Gd-Y, Yb-Y and Gd-Yb-Y co-doped samples are as high as ∼10.3 × 10−6 K−1 in temperature range between 200−1200 °C.

Graphical abstract Terpenoids are natural compounds predominantly present in plants. They have many pharmaceutical and/or nutritional functions, and have been widely applied in medical, food, and cosmetics industries. Recently, terpenoids have been used in the clinical treatment of COVID-19 due to the good antiviral activities. The increasing demand for terpenoids in international markets poses a serious threat to many plant species. For environmentally sustainable development, microbial cell factories have been utilized as the promising platform to produce terpenoids. Nevertheless, the bioproduction of most terpenoids cannot meet commercial requirements due to the low cost-benefit ratio until now. The biosynthetic potential of endophytes has gained attention in recent decades owing to the continual discovery of endophytes capable of synthesizing plant bioactive compounds. Accordingly, endophytes could be alternative sources of terpenoid-producing strains or terpenoid synthetic genes. In this review, we summarized the research progress describing the main and supporting roles of endophytes in terpenoid biosynthesis and biotransformation, and discussed the current problems and challenges which may prevent the further exploitation. This review will improve our understanding of endophyte resources for terpenoid production in industry in the future. The four main research interests on endophytes for terpenoid production. A: Isolation of terpenoid-producing endophytes; B: The heterologous expression of endophyte-derived terpenoid synthetic genes; C: Endophytes promoting their hosts’ terpenoid production. The blue dashed arrows indicate signal transduction; D: Biotransformation of terpenoids by endophytes or their enzymes. Key points • The mechanisms employed by endophytes in terpenoid synthesis in vivo and in vitro. • Endophytes have the commercial potentials in terpenoid bioproduction and biotransformation. • Synthetic biology and multiomics will improve terpenoid bioproduction in engineered cell factories.

Bacillus cereus is a common foodborne pathogen that can cause both gastrointestinal and nongastrointestinal diseases. In this study, we collected 603 meat and meat products from 39 major cities in China. The positive contamination rate of B. cereus in the collected samples was 26.37% (159/603), and the contamination level in 5.03% (8/159) positive samples exceeded 1100 most probable number/g. The detection rates of virulence genes were 89.7% for the nheABC gene group, 37.1% for the hblACD gene cluster, 82.3% for cytK-2, and 2.9% for cesB. Notably, all isolates presented with multiple antibiotic resistance, and 99.43% of isolates were resistant to five classes of antibiotics. In addition, the multilocus sequence typing results indicated that all isolates were rich in genetic diversity. Collectively, we conducted a systematic investigation on the prevalence and characterization of B. cereus in meat and meat products in China, providing crucial information for assessing the risk of B. cereus occurrence in meat and meat products.

Soil arbuscular mycorrhizal (AM) fungi were monitored in a 4-year experiment of nitrogen (N) and phosphorus (P) fertilization in three growing seasons (April, August, and November) under two successional stages (young and mature) in a subtropical forest of China. AM fungal extra-radical hyphal density was significantly affected by fertilization, season, and interactions between fertilization and season and between forest stage and season, but not by forest stage. The spore density of AM fungi was significantly affected by forest stage and season, but not by fertilization. Totally, 160 operational taxonomic units (OTUs) of AM fungi have been identified at a 97% sequence similarity level using Illumina MiSeq sequencing of the V4 region of the 18S rDNA. AM fungal Shannon diversity index, but not OTU richness, showed a positive response to P fertilization. The community composition of AM fungi was significantly influenced by P fertilization, but not by N fertilization, season, and forest stage. Phosphorus fertilization exhibited a negative impact on the relative abundance of the dominant Glomeraceae. This finding highlights that P availability has a strong effect on the community of AM fungi in the subtropical forest ecosystem.

Background: Mature lysostaphin (~28-kDa Lss) from Staphylococcus simulans proves effective in killing methicillin-resistant Staphylococcus aureus (MRSA) which is endemic in hospitals worldwide. Lss is Zn2+-dependent endopeptidase, but its bacteriolytic activity could be affected by exogenously added Zn2+. Objective: To gain greater insights into structural and functional impacts of Zn2+and Ni2+on Lss-induced bioactivity. Methods: Lss purified via immobilized metal ion-affinity chromatography was assessed for bioactivity using turbidity reduction assays. Conformational change of metal ion-treated Lss was examined by circular dichroism and intrinsic fluorescence spectroscopy. Co-sedimentation assay was performed to study interactions between Zn2+-treated Lss and S. aureus peptidoglycans. Metal ionbinding prediction and intermolecular docking were used to locate an extraneous Zn2+-binding site. Results: A drastic decrease in Lss bioactivity against S. aureus and MRSA was revealed only when treated with Zn2+, but not Ni2+, albeit no negative effect of diethyldithiocarbamate—Zn2+-chelator on Lss-induced bioactivity. No severe conformational change was observed for Lss incubated with exogenous Zn2+ or Ni2+. Lss pre-treated with Zn2+ efficiently bound to S. aureus cell-wall peptidoglycans, suggesting non-interfering effect of exogenous metal ions on cell-wall targeting (CWT) activity. In silico analysis revealed that exogenous Zn2+, but not Ni2+, preferably interacted with a potential extraneous Zn2+-binding site (His253, Glu318 and His323) placed near the Zn2+-coordinating Lssactive site within the catalytic (CAT) domain. Conclusion: Our present data signify the adverse influence of exogenous Zn2+ ions on Lss-induced staphylolytic activity through the exclusive presence within the CAT domain of an extraneous inhibitory Zn2+-binding site, without affecting the CWT activity.

Glioblastoma multiforme (GBM) is the most malignant primary tumour in the central nervous system, but the molecular mechanisms underlying its pathogenesis remain unclear. In this study, data set GSE50161 was used to construct a co‐expression network for weighted gene co‐expression network analysis. Two modules (dubbed brown and turquoise) were found to have the strongest correlation with GBM. Functional enrichment analysis indicated that the brown module was involved in the cell cycle, DNA replication, and pyrimidine metabolism. The turquoise module was primarily related to circadian rhythm entrainment, glutamatergic synapses, and axonal guidance. Hub genes were screened by survival analysis using The Cancer Genome Atlas and Human Protein Atlas databases and further tested using the GSE4290 and Gene Expression Profiling Interactive Analysis databases. The eight hub genes (NUSAP1, SHCBP1, KNL1, SULT4A1, SLC12A5, NUF2, NAPB, and GARNL3) were verified at both the transcriptional and translational levels, and these gene expression levels were significant based on the World Health Organization classification system. These hub genes may be potential biomarkers and therapeutic targets for the accurate diagnosis and management of GBM., The molecular mechanisms underlying the pathogenesis of glioblastoma multiforme remain unclear. In this study, data set GSE50161 was used to construct a co‐expression network for analysis. We found the two modules (dubbed brown and turquoise) and eight hub genes (NUSAP1, SHCBP1, KNL1, SULT4A1, SLC12A5, NUF2, NAPB and GARNL3 that were most strongly associated with GBM. These hub genes may be potential biomarkers and therapeutic targets for the accurate diagnosis and management of GBM.

Glycoside hydrolase family 2 (GH2) enzymes are generally composed of three domains: TIM-barrel domain (TIM), immunoglobulin-like β-sandwich domain (ISD), and sugar-binding domain (SBD). The combination of these three domains yields multiple structural combinations with different properties. Theoretically, the drawbacks of a given GH2 fold may be circumvented by efficiently reassembling the three domains. However, very few successful cases have been reported. In this study, we used six GH2 β-glucuronidases (GUSs) from bacteria, fungi, or humans as model enzymes and constructed a series of mutants by reassembling the domains from different GUSs. The mutants PGUS-At, GUS-PAA, and GUS-PAP, with reassembled domains from fungal GUSs, showed improved expression levels, activity, and thermostability, respectively. Specifically, compared to the parental enzyme, the mutant PGUS-At displayed 3.8 times higher expression, the mutant GUS-PAA displayed 1.0 time higher catalytic efficiency (kcat /Km ), and the mutant GUS-PAP displayed 7.5 times higher thermostability at 65°C. Furthermore, two-hybrid mutants, GUS-AEA and GUS-PEP, were constructed with the ISD from a bacterial GUS and SBD and TIM domain from fungal GUSs. GUS-AEA and GUS-PEP showed 30.4% and 23.0% higher thermostability than GUS-PAP, respectively. Finally, molecular dynamics simulations were conducted to uncover the molecular reasons for the increased thermostability of the mutant.

Begonia scorpiuroloba sp. nov., a new species in Begonia sect. Platycentrum (Begoniaceae) from southern Guangxi of China, is described and illustrated. Morphologically, it is mostly similar to B. pedatifida, but differs clearly by its narrower lobes, denser hairs on leaf surface, obtuse angle of leaf base, subequal tepals of female flowers and late flowering. This new species is endemic to Guangxi and is assigned to Endangered (EN) according to the IUCN Red List Categories and Criteria.

What is already known about this topic? The endemic status of schistosomiasis appeared to continuously decrease in China from 2015 to 2019. The snail species Oncomelania hupensis is the only intermediate host involved in the transmission of Schistosoma japonicum, and this snail’s geographic distribution is strictly consistent with that of schistosomiasis. What is added by this report? The snail’s habitats did not decrease significantly in China from 2015 to 2019, and some habitats have been newly detected or recurrent in some regions. Snail habitats among nine counties in Hunan and Jiangxi covered nearly half of the areas with snails. What are the implications for public health practice? Considering the situation of snail distribution, strategies and measures on snail control should focus on key areas. In addition, study of the origin and causes of the newly-detected snail habitats and recurrent areas with snails needs to be strengthened, and comprehensive measures should be taken to prevent the spread of snails.

The aim of this study was to evaluate the physicochemical properties and aroma differences of yellow pea flours fermented by five lactic acid bacteria (LAB) strains including two Lactiplantibacillus, two Lactobacillus, and one Lacticaseibacillus with different fermentation time. The cell population and the pH of pea flour slurry, as well as the proximate chemical composition, amino acids, thermal and pasting properties, surface morphology, and aromatic differences of fermented flours were characterized. The cell population of all strains except for Lactobacillus helveticus was observed to reach above 107 CFU mL−1 after 24 h of fermentation. The fermentation with Lactobacilli resulted in the increase of amino acids and ash contents, and the reduction of fat content. Rapid viscosity analysis indicated that short time (18 h) fermentation with L. helveticus drastically improved the pasting properties of the flours by facilitating starch granule expansion. The aromatic compounds of the fermented yellow pea flours were highly reliant on the strains and fermentation time. The untargeted metabolomics analysis with the aid of multivariate data analysis can discriminate the aroma differences among the fermented yellow pea flours. L. acidophilus fermentation led to the production of three aromatic compounds which may contribute to an improved aromatic profile.

Context Astragalus polysaccharin (APS), an extract of Astragalus propinquus Schischk, exerts antitumor effects in hepatocellular carcinoma (HCC). Objective This study investigated the mechanism of action of APS in HCC. Materials and methods Tumour-associated macrophages (TAMs) were treated with APS (0, 8, 16 mg/mL) for 24 h. APS (16 mg/mL)-treated TAMs were co-cultured with MHCC97H/Huh7 cells for 24 h. Finally, BALB/c nude mice were divided into PBS, APS (50 mg/kg), APS (100 mg/kg), APS (200 mg/kg) groups: mice were inoculated with Huh7 cells to construct tumour xenograft model, followed by administration of APS (50, 100, 200 mg/kg) or PBS daily for 30 days. Cell proliferation, migration, invasion, tumour growth, macrophage markers and proportions were measured. Results APS 16 mg/mL treatment enhanced the expression of M1 macrophage markers (iNOS, IL-1β and TNF-α) and M1 macrophage proportions, while reducing the expression of M2 macrophage markers (IL-10, Arg-1) and M2 macrophage proportions in TAMs. Moreover, the APS-mediated M1 phenotype of TAMs significantly repressed cell proliferation, migration and invasion of MHCC97H and Huh7 cells. Moreover, APS (50, 100, 200 mg/kg) enhanced M1 macrophage proportions and reduced M2 macrophage proportions in the tumour tissues, and thus inhibited tumour growth of HCC. Discussion and conclusions APS inhibits HCC-like phenotypes in a murine HCC model through repression of M2 polarization of TAMs. This work provides a novel theoretical basis for the application of APS in the clinical treatment of HCC.

Background Culicoides (Diptera: Ceratopogonidae) are vectors for many arboviruses. At least 20 species are considered as vectors or potential vectors of bluetongue virus (BTV) which cause bluetongue disease in ruminants. A BTV prevalence of 30–50% among cattle and goats in tropical southern Yunnan Province, China, prompted an investigation of the potential BTV vectors in this area. Methods Culicoides were collected by light trapping at three sites in the tropical region of Yunnan Province. Species were identified based on morphology and DNA sequences of cytochrome c oxidase subunit 1 (cox1). PCR and quantitative PCR following reverse transcription were used to test for the presence of BTV RNA in these specimens. Phylogenetic analysis was used to analyze the cox1 sequences of Culicoides specimens infected with BTV. Results Approximately 67,000 specimens of Culicoides were collected, of which 748 were tested for the presence of BTV. Five specimens, including two of Culicoides jacobsoni, one of C. tainanus and two of C. imicola, were identified as infected with BTV. No specimens of C. (subgenus Trithecoides) or C. oxystoma tested were positive for BTV infection. Conclusions To our knowledge this is the first report of C. jacobsoni as a potential BTV vector and the fourth report of an association between C. tainanus and BTV, as well as the first direct evidence of an association between BTV and C. imicola in Asia. A fourth potential cryptic species within C. tainanus was identified in this study. Further analysis is required to confirm the importance of C. jacobsoni and C. tainanus in BTV epidemiology in Asia. Graphical Abstract

What is already known about this topic? Over 90% of Oncomelania snails, the only intermediate host of Schistosoma japonicum, are distributed in the middle and low reaches of Yangtze River. Flooding can extend the distribution of Oncomelania snails and hence accelerate the transmission of schistosomiasis. What is added by this report? Although the dispersal of Oncomelania snails was negligible in north Poyang Lake after flooding in 2020, 2 samples of cattle feces with Schistosoma egg and 2 infected snails samples were indeed found. All four risk sites were distributed in Lushan County. Cattle feces were observed in the six out of seven field sites in Lushan County. What are the implications for public health practice? The present national control strategy focusing on control of infection source should be reinforced in Lushan and other schistosomiasis endemic areas. Overlaps of infected snails and cattle feces with Schistosoma egg were not observed, which called for intensive surveillance in Lushan County.

Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17. miR-143 was also investigated as miR-143 and miR-145 are co-transcribed and associated with decreased tumour growth. HCT116 colon cancer cells (CCC) were co-transfected with predicted ADAM17-regulating miRNAs and luciferase reporters controlled by ADAM17-3’UTR. Separately, pre-miR-143 processing by colonic cells was measured. miRNAs were quantified by RT-PCR. Tumours were induced with AOM/DSS in WT and transgenic mice (Tg) expressing pre-miR-143/miR-145 under villin promoter. HCT116 transfection with miR-145, −148a or −152, but not scrambled miRNA inhibited ADAM17 expression and luciferase activity. The latter was suppressed by mutations in ADAM17-3’UTR. Lysates from colonocytes, but not CCC, processed pre-miR-143 and mixing experiments suggested CCC lacked a competency factor. Colonic miR-143, miR-145, miR-148a, and miR-152 were downregulated in tumours and more moderately by feeding mice a Western diet. Tg mice were resistant to DSS colitis and had significantly lower cancer incidence and tumour multiplicity. Tg expression blocked up-regulation of putative targets of miR-143 and miR-145, including ADAM17, K-Ras, XPO5, and SET. miR-145, miR-148a, and miR-152 directly suppress colonocyte ADAM17 and are down-regulated in colon cancer. This is the first direct demonstration of tumour suppressor roles for miR-143 and miR-145 in an in vivo model of colonic tumorigenesis.

Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast., Bikaverin is a fungal-derived tetracyclic polyketide with antibiotic, antifungal and anticancer properties. Here, the authors employ various pathway engineering strategies to achieve high level production of bikaverin in baker’s yeast.

Traditional fermented soybean food has emerged as an important part of people's dietary structure because of the unique flavors and improved health benefit. During fermentation, the nutrients in soybean undergo a series of biochemical reactions catalyzed naturally by microorganism secreted enzymes. Thereafter, many functional and bioactive substances such as bioactive peptides, unsaturated fatty acids, free soy isoflavones, vitamins and minerals are produced, making fermented soy products more advantageous in nutrition and health. This review comprehensively discusses the historical evolution, distribution, traditional fermentation processing, main sources and characteristics of fermented strains, flavor components, nutritional properties, and biological activities of four traditional fermented soybean foods including douchi, sufu, dajiang, and soy sauce. In the end, we introduce four major challenges encountered by traditional fermented soybean foods including high salt content, formation of biogenic amine, the presence of pathogenic microorganisms and mycotoxins, and quality inconsistency. We conclude that the establishment of scientific quality standard and innovated fermentation processing is the potential solutions to combat the issues and improve the safety of traditional fermented soybean products.

Background Bacillus cereus is a foodborne pathogen commonly found in nature and food and can cause food spoilage and health issues. Although the prevalence of B. cereus in foods has been reported worldwide, the extent of contamination in edible fungi, which has become increasingly popular as traditional or functional food, is largely unknown. Here we investigated the prevalence, toxin genes’ distribution, antibiotic resistance, and genetic diversity of B. cereus isolated from edible fungi in China. Results Six hundred and ninety-nine edible fungi samples were collected across China, with 198 (28.3%) samples found to be contaminated by B. cereus, with an average contamination level of 55.4 most probable number (MPN)/g. Two hundred and forty-seven B. cereus strains were isolated from the contaminated samples. Seven enterotoxin genes and one cereulide synthetase gene were detected. The detection frequencies of all enterotoxin genes were ≥ 80%, whereas the positive rate of the cesB gene in B. cereus was 3%. Most isolates were resistant to penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and ansamycins, but were susceptible to penems, aminoglycosides, macrolides, ketolide, glycopeptides, quinolones, phenylpropanol, tetracyclines, lincosamides, streptogramins, and nitrofurans. Meanwhile, 99.6% of all isolates displayed multiple antimicrobial resistance to three or more classes of antimicrobials. Using genetic diversity analysis, all isolates were defined in 171 sequence types (STs), of which 83 isolates were assigned to 78 new STs. Conclusions This study provides large-scale insight into the prevalence and potential risk of B. cereus in edible fungi in China. Approximately one-third of the samples were contaminated with B. cereus, and almost all isolates showed multiple antimicrobial resistance. Detection frequencies of all seven enterotoxin genes were equal to or more than 80%. These new findings may indicate a need for proper pre-/post-processing of edible fungi to eliminate B. cereus, thereby preventing the potential risk to public health.

Yttria stabilized hafnia (Hf0.84Y0.16O1.92, YSH16) coatings were sprayed by atmospheric plasma spraying (APS). The effects of thermal aging at 1400 °C on the microstructures, mechanical properties and thermal conductivity of the coatings were studied. The results show that the as-sprayed coating was composed of the cubic phase, and the nano-sized monoclinic (M) phase was precipitated in the annealed coating. The presence of M phase effectively constrained the sintering of the coating due to its superior sintering-resistance. The Young's modulus kept at a nearly same level of ~78 GPa even after annealing, and the coating annealed for 6 h yielded a maximum value of hardness but revealed a declining tendency in the Vicker's hardness with prolonged sintering time. The thermal conductivity increased from 0.8-0.95 W m-1 K-1 at as-sprayed state to 1.6 W m-1 K-1 after annealing at 1400 °C for 96 h. The dual-phase coating is promising to serve at temperatures above 1400 °C due to its excellent thermal stability and mechanical properties.

Yeast productivity in lignocellulosic ethanol fermentation is clearly impeded by stress. Enhancing the robustness of xylose-fermenting yeast is important for improving lignocellulosic ethanol production. In this study, the glutathione biosynthesis pathway and acetic acid degradation pathway were strengthened to enhance yeast tolerance to stress due to elevated reactive oxygen species (ROS) and acetic acid. Dynamic feedback regulation of the anti-stress genetic circuits was achieved using stress-driven promoters discovered from the transcriptome to maintain low intracellular ROS, relieve the metabolic burden, and ultimately improve the robustness and ethanol production of yeast. The cell growth, xylose utilization and ethanol production of the engineered strain were enhanced under both stress and nonstress conditions. The engineered strain showed 49.5% and 17.5% higher ethanol productivity in laboratory media and industrial lignocellulosic media, respectively, at 36 °C compared with the parent strain. This study provides novel insights on the rational design and construction of feedback genetic circuits for dynamically improving yeast robustness.

The geographical distribution patterns of Asian Metaeuchromius are analysed with MaxEnt and ArcGIS based on known localities and nineteen environmental variables. The results suggest that the most highly suitable area of the genus located in southeastern China. Precipitation of the warmest quarter (Bio18) and temperature seasonality (Bio4) are the most significant variables affecting geographical distribution Metaeuchromius. Furthermore, a new species from Jiangxi Province, southeast China is added to the genus, Metaeuchromius grandispinata Li, sp. nov. Its habitus, tympanic organs and genitalia are illustrated, and two maps showing geographical distribution patterns of Metaeuchromius in Asia are provided.

Downy mildew is one of the most serious diseases threatening grapevine cultivation. The PYR/PYL/RCAR proteins, which act as abscisic acid (ABA) receptors, are multifunctional, highly conserved, and reportedly play a crucial role in plant stress resistance in the ABA signaling pathway. In this study, we cloned a putative abscisic acid receptor gene, VvPYL4, from the ‘Beta’ grapevine cultivar. An analysis of the subcellular localization demonstrated that overexpressed VvPYL4 was localized in both the cytoplasm and the nucleus. The resistance of grapevine cultivars to downy mildew increased after the application of the exogenous hormones MeJA and ABA. The expression of VvPYL4 was significantly induced when exposed to Plasmopara viticola, MeJA, and ABA. The transcript of the VvPYL4 gene in ‘Beta’ grapevine leaves treated with tobacco rattle virus-induced gene silencing (VIGS) was significantly down-regulated. Silencing VvPYL4 had a slight effect on P. viticola resistance. Furthermore, silencing VvPYL4 significantly altered the transcripts of ABA and JA responsive genes, including the ABA signaling pathway-related genes ABF1, SnRK2.2, and PP2C2, as well as the genes related to the JA signaling pathway, MYC2, JAR1, and JAZ. Altogether, the data provide new evidence that VvPYL4 positively regulates grapevine response to downy mildew. This study also discusses the regulation mechanism of VvPYL4 on ABA and JA signaling transduction. Finally, these results provide a basis for additional research on the mechanisms behind grapevine resistance to downy mildew. Silencing VvPYL4 impaired resistance to P. viticola, and this was associated with inhibited the expression of the ABA and JA signaling pathway-related genes. P. viticola, MeJA, and ABA induced the up-regulated expression of VvPYL4.

The genus Tetracona has two species with an Australian distribution. The present study aims to record the genus from China for the first time and to add a third species, T. multispina Jie & Li, sp. nov. to the genus. The new species can be distinguished from the congeners by the antemedial line connecting the postmedial line near the dorsum in the hindwing, and the phallus with a cluster of spine-like cornuti in the male genitalia. Images of the habitus, tympanal organs and male genitalia are provided for the new species.

Purpose This study aimed to examine pathogenic mutation within one Chinese family of five-generations suffering from autosomal dominant cataract. Methods Next-generation sequencing and Sanger sequencing were used to find the pathogenic variants. Results A rare mutation, c.563G > A, in CRYBB2 gene was found in the proband that showed symptom of non-syndromic congenital autosomal dominant cataract. This mutation had been found in all affected individuals and in one healthy infant, but it did not exist between two individuals who did not develop such disease in that family, as well as in 100 healthy subjects who showed no relation with that family. Cataracts in this family varied with different severity of lens opacities and elongation of axial length. Conclusion One missense mutation c.563G > A is reported in the CRYBB2 gene among one Chinese family suffering from early-onset cataract, and associated novel phenotypes are the elongation of axial length and the types of cataract. Our results expand the spectrum of associated phenotypes of CRYBB2 mutation.

Background Cortical dopaminergic systems are critically involved in prefrontal cortex (PFC) functions, especially in working memory and neurodevelopmental disorders such as schizophrenia. GSK-3β (glycogen synthase kinase-3β) is highly associated with cAMP (cyclic adenosine monophosphate)–independent dopamine D2 receptor (D2R)-mediated signaling to affect dopamine-dependent behaviors. However, the mechanisms underlying the GSK-3β modulation of cognitive function via D2Rs remains unclear. Methods This study explored how conditional cell-type–specific ablation of GSK-3β in D2R+ neurons (D2R-GSK-3β−/−) in the brain affects synaptic function in the medial PFC (mPFC). Both male and female (postnatal days 60–90) mice, including 140 D2R, 24 D1R, and 38 DISC1 mice, were used. Results This study found that NMDA receptor (NMDAR) function was significantly increased in layer V pyramidal neurons in mPFC of D2R-GSK-3β−/− mice, along with increased dopamine modulation of NMDAR-mediated current. Consistently, NR2A and NR2B protein levels were elevated in mPFC of D2R-GSK-3β−/− mice. This change was accompanied by a significant increase in enrichment of activator histone mark H3K27ac at the promoters of both Grin2a and Grin2b genes. In addition, altered short- and long-term synaptic plasticity, along with an increased spine density in layer V pyramidal neurons, were detected in D2R-GSK-3β−/− mice. Indeed, D2R-GSK-3β−/− mice also exhibited a resistance of working memory impairment induced by injection of NMDAR antagonist MK-801. Notably, either inhibiting GSK-3β or disrupting the D2R-DISC1 complex was able to reverse the mutant DISC1-induced decrease of NMDAR-mediated currents in the mPFC. Conclusions This study demonstrates that GSK-3β modulates cognition via D2R-DISC1 interaction and epigenetic regulation of NMDAR expression and function.

The bluegrass webworm moth Parapediasia teterrella (Zincken, 1821) is a notorious pest that is native to North America. However, it has invaded East Asia and has caused serious economic losses in China and Japan. The objective of this paper is to analyse the potential geographic distribution of P. teterrella in East Asia with MaxEnt, using predictor variables related to temperature and precipitation. It is suggested that this species has potential to establish in Southeast China, most areas of Jeollanam-do, eastern coastal region of South Korea, and most areas of Japan. Furthermore, we applied the Jackknife test to evaluate the significance of climatic variables in modelling the potential distribution of P. teterrella. The result indicates that annual mean temperature (Bio1), mean temperature of the coldest quarter (Bio11) and precipitation of the coldest quarter (Bio19) mainly affect its geographical distribution. A map showing the potential distribution of P. teterrella in East Asia is provided, and morphological diagnosis of the species is also given.

High-dose radiation activates caspases in tumor cells to produce abundant DNA fragments for DNA sensing in antigen-presenting cells, but the intrinsic DNA sensing in tumor cells after radiation is rather limited. Here we demonstrate that irradiated tumor cells hijack caspase 9 signaling to suppress intrinsic DNA sensing. Instead of apoptotic genomic DNA, tumor-derived mitochondrial DNA triggers intrinsic DNA sensing. Specifically, loss of mitochondrial DNA sensing in Casp9-/- tumors abolishes the enhanced therapeutic effect of radiation. We demonstrated that combining emricasan, a pan-caspase inhibitor, with radiation generates synergistic therapeutic effects. Moreover, loss of CASP9 signaling in tumor cells led to adaptive resistance by upregulating programmed death-ligand 1 (PD-L1) and resulted in tumor relapse. Additional anti-PD-L1 blockade can further overcome this acquired immune resistance. Therefore, combining radiation with a caspase inhibitor and anti-PD-L1 can effectively control tumors by sequentially blocking both intrinsic and extrinsic inhibitory signaling.

Transfer RNAs (tRNAs) are products of RNA polymerase III (Pol III) and essential for mRNA translation and ultimately cell growth and proliferation. Whether and how individual tRNA genes are specifically regulated is not clear. Here, we report that SOX4, a well-known Pol II-dependent transcription factor that is critical for neurogenesis and reprogramming of somatic cells, also directly controls, unexpectedly, the expression of a subset of tRNA genes and therefore protein synthesis and proliferation of human glioblastoma cells. Genome-wide location analysis through chromatin immunoprecipitation-sequencing uncovers specific targeting of SOX4 to a subset of tRNA genes, including those for tRNAi Met . Mechanistically, sequence-specific SOX4-binding impedes the recruitment of TATA box binding protein and Pol III to tRNA genes and thereby represses their expression. CRISPR/Cas9-mediated down-regulation of tRNAi Met greatly inhibits growth and proliferation of human glioblastoma cells. Conversely, ectopic tRNAi Met partially rescues SOX4-mediated repression of cell proliferation. Together, these results uncover a regulatory mode of individual tRNA genes to control cell behavior. Such regulation may coordinate codon usage and translation efficiency to meet the demands of diverse tissues and cell types, including cancer cells.

Tylopilus jiangxiensis is described as a new species characterized by its small basidiomata, yellowish brown pileal and stipe surface, pallid to pinkish hymenophore, smooth stipe surface and white context without color change when bruised. Molecular phylogenetic analyses based on five gene makers (ITS, nrLSU, tef1-α, rpb1 and rpb2) confirmed it as a novel member of the genus Tylopilus s. str. Its morphological descriptions and illustrations are provided.

Objective: Longshengzhi capsule (LSZC) is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction (BYHWD), and is approved by the China Food and Drug Administration for treating stroke-induced disability and vascular diseases. Herein, we examined the pharmacodynamics, anti-apoptotic and anti-oxidant actions, and potential mechanisms of action of LSZC following stroke in rats. Methods: Permanent middle cerebral artery occlusion (MCAO) was used as an ischemic stroke model. LSZC was administered intragastrically. We examined the survival rate, bodyweight, and neurological deficits in stroke rats. Brain infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Brain pathology was examined using hematoxylin and eosin staining, Nissl staining, and TdT-mediated dUTP Nick-End Labeling staining. Malondialdehyde, catalase, superoxide dismutase, and glutathione levels were examined by commercial kits. Expression of Nrf2, heme oxygenase-1, Bax, Bcl-2, cleaved caspase-3, and caspase-3 proteins in brain tissue was measured by Western blot. Results: LSZC markedly improved the survival rate and bodyweight, and reduced infarct volume and neurological deficit scores, in MCAO stroke rats. LSZC also significantly attenuated oxidative stress, as indicated by decreased expression of malondialdehyde, and upregulation of Nrf2, heme oxygenase-1, catalase, superoxide dismutase, and glutathione. Moreover, LSZC significantly decreased apoptosis, including a decrease in Bax and cleaved caspase-3 expression, and an increase in Bcl-2, as well as a reduction in numbers of apoptotic neurons. Conclusion: LSZC treatment is neuroprotective against ischemic stroke, potentially via reducing oxidative stress and apoptosis. The Nrf2 and apoptotic signaling pathways may play important roles in the antioxidant and anti-apoptotic actions of LSZC. Keywords: Longshengzhi capsule, Middle cerebral artery occlusion, Oxidative stress, Apoptosis, Cerebral protective

Objective: This study assessed whether Chinese herbal medicine (CHM) combined with probiotics/synbiotics for irritable bowel syndrome - diarrhea (IBS-D) was more effective and safer than probiotics/synbiotics alone. Methods: Ten databases were searched for randomized control trials (RCTs) of IBS-D as diagnosed by Manning or Rome criteria. Trials comparing probiotics and probiotics with CHM were included. The Cochrane risk of bias (ROB) was evaluated for each trial. RevMan 5.3 was used to conduct a meta-analysis. Results: Twenty-six RCTs were included (25 Chinese, 1 English), involving 2045 participants. Meta-analysis was conducted on two outcomes: overall symptom improvement and relapse. CHM combined with live Bifidobacterium and Lactobacillus preparations reduced relapse rate (RR 0.28, 95%CI 0.15–0.52, 3 trials, n = 205) compared with probiotics alone. The subgroup analysis showed the benefit of CHM prescriptions based on soothing liver and invigorating spleen (1.28, 1.14–1.44, 3, 244), invigorating spleen and resolving dampness (1.20, 1.03–1.41, 2, 128), or warming and invigorating spleen and kidney formulae (1.27, 1.09–1.46, 2, 210) combined with triple Bifidobacterium preparations than the same probiotics alone which improved overall symptoms for IBS-D. There was unclear bias in almost domains of ROB. Most studies had a high risk of bias due to lack of blinding of investigator and participants, and selective reporting. Conclusions: This study showed that CHM combined with probiotics may reduce relapse rate by 72%, and improve overall symptoms of IBS-D (as diagnosed by Rome II and III) compared to probiotics alone. From the limited subgroup analysis, only soothing liver and invigorating spleen formulae, represented by Tongxie Yaofang, added to triple Bifidobacterium preparations may be superior to the single preparations in terms of overall symptoms. However, due to the poor methodological quality and small sample size of the trials, these findings must be interpreted with caution. Keywords: Chinese herbal medicine, Probiotic, Synbiotic, Irritable bowel syndrome, Randomized controlled trials, Systematic review, Meta-analysis