Metagenomic analysis revealed the association between gut microbiota and different ovary responses to controlled ovarian stimulation.

The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI) < 0.5 and 25 IVF cycles with FOI ≥ 0.5 were included in this study. Baseline demographic characteristics were compared between the two groups. Metagenomic sequencing was performed to analyze fecal microbial community profiles. Mice were used to evaluate the effect of Bifidobacterium_longum on ovarian response to stimulation. Compared with FOI < 0.5 group, women in group with FOI ≥ 0.5 had significant more oocytes retrieved (p < 0.01). Prevotella_copri, Bateroides_vulgatus, Escherichia_coli and Bateroides_stercoris were more abundant in FOI < 0.5 group while Bifidobacterium_longum, Faecalibacterium_prausnitzii, Ruminococcus_gnavus and Bifidobacterium_pseudocatenula were more abundant in FOI ≥ 0.5 group. After adjusting for women's age and BMI, Pearson correlation analysis indicated alteration of gut microbiome was related with serum E2, FSH, number of oocytes retrieved and clinical pregnancy rate. Animal study showed ovarian response will be improved after Bifidobacterium_longum applied. An increased abundance of Bacteroidetes and Prevotella copri, as well as a decreased abundance of Bifidobacterium longum, have been found to be associated with poor ovarian responsiveness. Changes in gut microbiomes have been observed to be correlated with certain clinical characteristics. The potential enhancement of ovarian response may be facilitated by the integration of Bifidobacterium longum.

Mechanism of ultrasound-induced soybean/egg white composite gelation: Gel properties, morphological structure and co-aggregation kinetics.

This study aims to develop ultrasound-assisted acid-induced egg white protein (EWP)-soy protein isolate (SPI) composite gels and to investigate the mechanistic relationship between the co-aggregation behavior of composite proteins and gel properties through aggregation kinetics monitored continuously by turbidity. The results showed that the inclusion of EWP caused the attenuation of gel properties and maximum aggregation (Amax) because EWP could aggregate with SPI at a higher rate (Kapp), which impeded the interaction between SPI and the formation of a continuous gelling network. In the EWP-dominated system, SPI with higher molecular weights also increased the fractal dimension of gels. Ultrasound improved properties of composite gels, especially the SPI-dominated system. After ultrasound treatment, the small, uniform size of co-aggregates and the decrease in potential led to an increase in the aggregation rate and formation of dense particles, consistent with an increase in gelation rate and texture properties. Excessively fast aggregation generated coarse chains and more pores. Still, the exposure of free sulfhydryl groups assisted the gel structure units to form a compact network through disulfide bonding. On the whole, the study could provide theoretical support for a deeper understanding on the interaction mechanism and gelation of composite proteins.

Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition.

The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10. Loss of AHR or ALDH1A3 largely abrogates IDA-promoted tumour development both in vitro and in vivo. It is interesting that P. anaerobius is significantly enriched in patients with colorectal cancer (CRC). IDA treatment or implantation of P. anaerobius promotes CRC progression in both xenograft model and ApcMin/+ mice. Together, our findings demonstrate that targeting the IDA-AHR-ALDH1A3 axis should be promising for ferroptosis-related CRC treatment.

Inhibition of FLT1 Attenuates Neurodevelopmental Abnormalities and Cognitive Impairment in Offspring Caused by Maternal Prenatal Stress.

Fms-like tyrosine kinase 1 (FLT1) has been shown to regulate processes such as angiogenesis, neurogenesis, and cognitive impairment. However, the role of FLT1 in prenatal stress (PS) is unclear. The purpose of this study was to investigate the role of FLT1 in PS mothers and their offspring. Wire mesh restrainers were used to construct PS rat model. The levels of FLT1, IL-1ß, IL-6, and ROS in clinical samples and rat samples were detected by qRT-PCR, ELisa kit, and DCFH-DA fluorescence kit. Morris water maze assay and forced swimming assay were used to test the cognitive function of offspring young rats. The apoptosis level of hippocampal neurons and the expression of NMDARs were detected by MTT assay, TUNEL assay, and Western blot. The results showed that FLT1 was upregulated in PS mothers and positively correlated with PS degree. The level of FLT1 was elevated in PS model rats. Knockdown of FLT1 reduced maternal ROS and MDA levels and increased SOD levels in PS rats. Knockdown of FLT1 also reduced the secretion of IL-1ß, IL-6, and cortisol in PS rats. Inhibition of FTL1 alleviated cognitive impairment in PS offspring pups. Inhibition of FTL1 reduced hippocampal neuronal apoptosis and increased the expression of NMDARs in PS progeny. In conclusions, we demonstrated that knockdown of FLT1 inhibits maternal oxidative stress, inflammation, and cortisol secretion in PS rats. In addition, knockdown of FLT1 also alleviated cognitive dysfunction and neurodevelopmental abnormalities in PS offspring pups.

c-Jun as a one-way valve at the naive to primed interface.

BACKGROUND: c-Jun is a proto-oncogene functioning as a transcription factor to activate gene expression under many physiological and pathological conditions, particularly in somatic cells. However, its role in early embryonic development remains unknown. RESULTS: Here, we show that c-Jun acts as a one-way valve to preserve the primed state and impair reversion to the naïve state. c-Jun is induced during the naive to primed transition, and it works to stabilize the chromatin structure and inhibit the reverse transition. Loss of c-Jun has surprisingly little effect on the naïve to primed transition, and no phenotypic effect on primed cells, however, in primed cells the loss of c-Jun leads to a failure to correctly close naïve-specific enhancers. When the primed cells are induced to reprogram to a naïve state, these enhancers are more rapidly activated when c-Jun is lost or impaired, and the conversion is more efficient. CONCLUSIONS: The results of this study indicate that c-Jun can function as a chromatin stabilizer in primed EpiSCs, to maintain the epigenetic cell type state and act as a one-way valve for cell fate conversions.

Methylation and expression quantitative trait loci rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene are associated with opioid use disorder.

Opioid use disorder (OUD) is a chronic and relapsing brain disease that results in significant mortality worldwide. Genetic factors are estimated to contribute to 40%-60% of the liability, with polymorphisms of opioid receptor genes implicated in this disorder. However, the mechanisms underlying these associations are not yet fully understood. In the present study, we first examined the methylation levels in the promoter region of the OPRM1, OPRD1, and OPRK1 genes in 111 healthy controls (HCs) and 120 patients with OUD, and genotyped three tag SNPs in these genes. Correlations between these SNPs and the methylation levels of the CpG sites and expression levels of the genes were analyzed. After identifying the mQTLs and eQTLs, we determined the associations between the mQTLs/eQTLs and susceptibility to and characteristics of OUD in 930 HCs and 801 patients with OUD. Our results demonstrated that SNPs rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene were both mQTLs and eQTLs. We observed unique correlations between mQTLs and methylation levels of several CpG sites in the OUD group compared to the HC group. Interestingly, both the two mQTLs and eQTLs were associated with the susceptibility to OUD. In conclusion, we suppose that mQTLs and eQTLs in genes may underlie the associations between certain risk genetic polymorphisms and OUD. These mQTLs and eQTLs could potentially serve as promising biomarkers for better management of opioid misuse.

Metagenomic sequencing reveals altered gut microbial compositions and gene functions in patients with non-segmental vitiligo.

BACKGROUND: Vitiligo has been correlated with an abnormal gut microbiota. We aimed to systematically identify characteristics of the gut microbial compositions, genetic functions, and potential metabolic features in patients with non-segmental vitiligo. METHODS: Twenty-five patients with non-segmental vitiligo and 25 matched healthy controls (HCs) were enrolled. Metagenomic sequencing and bioinformatic analysis were performed to determine the gut microbiota profiles. Differences in gut microbiota diversity and composition between patients with vitiligo and HCs were analyzed. Gene functions and gut metabolic modules were predicted with the Kyoto Encyclopedia of Gene and Genomes (KEGG) and MetaCyc databases. RESULTS: Compared with HCs, alpha diversity of intestinal microbiome in vitiligo patients was significantly reduced. At the species level, the relative abundance of Staphylococcus thermophiles was decreased, and that of Bacteroides fragilis was increased in patients with vitiligo compared with those of the HCs. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed representative microbial markers of Lachnospiraceae_bacterium_BX3, Massilioclostridium_coli, TM7_phylum_sp_oral_taxon_348 and Bacteroides_fragilis for patients with vitiligo. KEGG gene function analysis showed that the NOD-like receptor signaling pathway was significantly enriched in patients with vitiligo. Gut metabolic modules (GMMs) analysis showed that cysteine degradation was significantly down-regulated, and galactose degradation was up-regulated in patients with vitiligo. A panel of 28 microbial features was constructed to distinguish patients with vitiligo from HCs. CONCLUSIONS: The gut microbial profiles and genetic functions of patients with vitiligo were distinct from those of the HCs. The identified gut microbial markers may potentially be used for earlier diagnosis and treatment targets.

First report of Fusarium cugenangense causing root rot of tea plants (Camellia sinensis) in China.

Root rot is an important disease of tea plants owing to its unobvious early symptoms and permanent damage (Huu et al. 2016). In 2019, 5% of tea plants displayed symptoms consistent with root rot in a tea plantation (28°09'N, 113°13'E) located in Changsha city, Hunan province of China. The symptoms of the diseased tea plants ranged from wilting leaves to entirely dead. The roots had black lesions and rot typical of this disease. Symptomatic roots were collected, washed with water and disinfected with 75% ethanol, then cut into pieces and sterilized with 0.1% mercuric chloride for 30 s, 75% ethanol for 1 min, and rinsed with sterile water five times. After drying on sterilized filter paper, root tissues were cultured on potato dextrose agar (PDA) medium at 25 oC for 7 days in the dark. Four isolates, CAGF1, CAGF2, CAGF3, and CAGF4 were purified by selecting single spores. All isolates were subjected to a pathogenicity test. A conidial suspension of each strain was collected at a concentration of 2×106 conidia/mL. For the pathogenicity test, two-year-old field grown tea plants were transplanted in plastic pots containing 240 g of the rice grain-bran mixture (inoculated with 4 mL of conidial suspension and cultured for 14 days) and 960 g of sterilized soil (Huu et al. 2016). The pots without inoculated mixture served as control group. All the pots were kept in illumination incubators at 25 oC and a 12L:12D photoperiod. The pathogenicity test for each strain was repeated three times with three repetitions. Only strain CAGF1 exhibited pathogenicity to tea plants. Symptoms appeared on the third day post inoculation (dpi) and gradually worsened by the 7 dpi. On the 14 dpi, most leaves had died and the roots were black and partially rotten, similar to field symptoms. The reisolated fungus from potted roots was identified as CAGF1 based on ITS region and colony morphology, while isolation was attempted, CAGF1 was not isolated from the control plants, which fulfilled Koch's postulates. On PDA, the colony center of CAGF1 was purple with white margin, while on carnation leaf agar (CLA) medium was white. On CLA medium, macroconidia have 0 to 3 septa, measured 19.1 µm to 41.2 µm × 4.2 µm to 5.4 µm (mean= 31.2 µm × 4.8 µm, n=30). The microconidia were measured as 6.7 µm to 12.8 µm × 2.4 µm to 4.9 µm (mean= 10.1 µm × 3.3 µm, n=30), with 0 to 1 septa. And the chlamydospores were measured as 6.0 to 9.7µm (mean= 7.7µm, n=30). Morphologically, strain CAGF1 was identified as Fusarium oxysporum (Leslie and Summerell 2006). Additionally, the genomic DNA of strain CAGF1 was extracted by cetyltrimethylammonium bromide (CTAB) method, the internal transcribed spacer (ITS), elongation factor 1 alpha (EF-1α) and second largest subunit of RNA polymerase II (RPB2) were amplified using the primers ITS1/ITS4 (White et al. 1990), EF-1/EF-2 (Geiser et al. 2004) and fRPB2-5F/fRPB2-7cR (Liu et al. 1999), respectively. Sequences were deposited in GenBank (ITS, OK178562.1; EF-1α, OK598121.1; RPB2, OP381476.1). BLASTn searches revealed that strain CAGF1 was 100% (ON075522.1 for ITS and JX885464.1 for RPB2) and 99.6% (JQ965440.1 for EF-1α) identical to Fusarium oxysporum species complex (FOSC). Based on phylogenetic analysis, the strain CAGF1 was identified as Fusarium cugenangense, belonging to FOSC. To our knowledge, this is the first report of F. cugenangense causing root rot of tea plants in China. The findings are important for the management of this root rot and the improvement of economic benefits of tea cultivation.

Carbon nitride nanotubes anchored with Cu(I) triggers peracetic acid activation with visible light for removal of antibiotic contaminants: Probing mechanisms of non-radical pathways and identifying active sites.

The peracetic acid (PAA)-activation process has attracted much attention in wastewater treatment. However, the low electron efficiency at the interface between heterogeneous catalysts and PAA has affected its practical application. For this study, we developed a carbon nitride hollow-nanotube catalysts with dispersed Cu(I) sites (Cu(I)-TCN) for the photocatalytic activation of PAA for antibiotics degradation. The obtained Cu(I)-TCN catalyst demonstrated an enhanced capacity for visible light harvesting along with increased charge transfer rates. Specifically, the developed Cu(I)-TCN/visible light/PAA system was able to completely remove antibiotics within 20 min, with a kinetic constant that was 25 times higher than a Cu(I)-TCN/visible light system, and 83 times higher than Cu(I)-TCN/PAA systems. Scavenging experiment and electron paramagnetic resonance (EPR) indicated that singlet oxygen was dominant reactive specie for sulfisoxazole (SIZ) removal. Besides, electrochemical tests and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy verified that the electron transfer efficiency of PAA activation was promoted due to the formation of inner-sphere interactions between PAA and Cu(I)-TCN, resulting in the quick removal of antibiotics. Further, after exposure to visible light, the Cu(I)-TCN excited photogenerated electrons which supplemented the electrons consumed in the reaction and drove the valence cycle of Cu ions. Overall, this research offered novel insights into the non-radical pathway for heterogeneous visible light-driven advanced oxidation processes and their potential for practical wastewater remediation.

c-JUN is a barrier in hESC to cardiomyocyte transition.

Loss of c-JUN leads to early mouse embryonic death, possibly because of a failure to develop a normal cardiac system. How c-JUN regulates human cardiomyocyte cell fate remains unknown. Here, we used the in vitro differentiation of human pluripotent stem cells into cardiomyocytes to study the role of c-JUN. Surprisingly, the knockout of c-JUN improved cardiomyocyte generation, as determined by the number of TNNT2+ cells. ATAC-seq data showed that the c-JUN defect led to increased chromatin accessibility on critical regulatory elements related to cardiomyocyte development. ChIP-seq data showed that the knockout c-JUN increased RBBP5 and SETD1B expression, leading to improved H3K4me3 deposition on key genes that regulate cardiogenesis. The c-JUN KO phenotype could be copied using the histone demethylase inhibitor CPI-455, which also up-regulated H3K4me3 levels and increased cardiomyocyte generation. Single-cell RNA-seq data defined three cell branches, and knockout c-JUN activated more regulons that are related to cardiogenesis. In summary, our data demonstrated that c-JUN could regulate cardiomyocyte cell fate by modulating H3K4me3 modification and chromatin accessibility and shed light on how c-JUN regulates heart development in humans.

Strategy for improvement of molecular oxygen activation capacity of PPECu by chlorine doping for water decontamination.

The activation of molecular oxygen and generation of reactive oxygen species (ROS) play important roles in the efficient removal of contaminants from aqueous ecosystems. Herein, using a simple and rapid solvothermal process, we developed a chlorine-doped phenylethynylcopper (Cl/PPECu) photocatalyst and applied it to visible light degradation of sulfamethazine (SMT) in aqueous media. The Cl/PPECu was optimized to have a 2.52 times higher steady-state concentration of O2•- (3.62 × 10-5 M) and a 28.87 times higher degradation rate constant (0.2252 min-1) for SMT compared to pure PPECu. Further, the effectiveness of Cl/PPECu in treating sulfonamide antibiotics (SAs) in real water systems was verified through an investigation involving natural water bodies, SAs, and ambient sunlight. The energy band structure, DFT calculation and correlation heat map indicated that the addition of chlorine modulated the local electronic structure of PPECu, leading to an improvement in the electron-hole separation, enhanced the O2 activation, and promoted the generation of ROSs. This study not only puts forward innovative ideas for the eco-compatible remediation of environmental pollution using PPECu, but also sheds new light on the activation of oxygen through elemental doping.

Simplified synthesis of direct Z-scheme Bi2WO6/PhC2Cu heterojunction that shows enhanced photocatalytic degradation of 2,4,6-TCP: Kinetic study and mechanistic insights.

For this work, we employed n-type Bi2WO6 and p-type PhC2Cu to formulate a direct Z-scheme Bi2WO6/PhC2Cu (PCBW) photocatalyst via simplified ultrasonic stirring technique. An optimal 0.6PCBW composite exhibited the capacity to rapidly photodegrade 2,4,6-TCP (98.6% in 120 min) under low-power blue LED light, which was 8.53 times and 12.53 times faster than for pristine PhC2Cu and Bi2WO6, respectively. Moreover, electron spin resonance (ESR), time-resolved PL spectra, and quantitative ROS tests indicated that the PCBW enhanced the separation capacity of photocarriers. It also more readily associated with dissolved oxygen in water to generate reactive oxygen species (ROS). Among them, the ability of PCBW to produce ·O2- in one hour was 12.07 times faster than for pure PhC2Cu. In addition, the H2O2 formation rate and apparent quantum efficiency of PCBW are 10.73 times that of PhC2Cu, which indicates that PCBW not only has excellent photocatalytic performance, but also has outstanding ROS production ability. Furthermore, Ag photodeposition, in situ X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations were utilized to determine the photogenerated electron migration paths in the PCBW, which systematically confirmed that Z-scheme heterojunction were successfully formed. Finally, based on the intermediate products, three potential 2,4,6-TCP degradation pathways were proposed.

Key role of Fe(VI)-activated Bi2WO6 in the photocatalytic oxidation of sulfonamides: Mediated electron transfer mechanism.

The widespread use of sulfonamides (SAs) in animals and human infections has raised significant concerns regarding their presence in ambient waterways and potential for inducing antimicrobial resistance. Herein, we report on the capacity of ferrate (VI) (FeVIO42-, Fe(VI)) to facilitate the photocatalytic degradation of sulfamethazine (SMT) via bismuth tungstate (Bi2WO6, BWO) under blue LED light (Vis/BWO/Fe(VI)) exposure, at rates that were 45-fold faster than BWO photocatalysis. Both the stepwise and time-series addition of Fe(VI) contributed to the degradation. Multiple lines of evidence confirmed that the common reactive species (RSs) in BWO-based photocatalytic systems and Fe(VI)-involved systems (e.g., •OH/h+, O2•-, 1O2 and Fe(V)/Fe(IV)) played subtle roles in our study system. Herein, for the first time, it was discovered that the precursor complex (BWO-Fe(V)/Fe(IV)* )) was the main contributor to induce electron transfer of SAs through the "conductive bridge" effect of BWO. The studied system was able to effectively degrade SMT in synthetic hydrolyzed urine (SHU) with low interference from background substances in water. This work not only offers a novel facilitation strategy for BWO, but also holds a great application prospect for contamination remediation in urine.

Association between methylation in the promoter region of the GAD2 gene and opioid use disorder.

DNA methylation is one of the epigenetic mechanisms involved in opioid use disorder. GAD2 is a key catalyticase in gamma amino butyric acid (GABA) synthesis from glutamate, that is implicated in opioid-induced rewarding effect. To reveal the relationship and the underlying mechanism between GAD2 gene methylation and opioid use disorder, we first examined and compared the methylation levels in the promoter region of the GAD2 gene in peripheral blood between 120 patients with opioid use disorder and 110 healthy controls by using a targeted approach. A diagnostic model with methylation biomarkers was established to distinguish opioid use disorder and healthy control groups. Correlations between methylation levels in the promoter region of the GAD2 gene and the duration and dosage of opioid use were then determined. Finally, the transcription factors that potentially bind to the target sequences including the detected CpG sites were predicted with the JASPAR database. Our results demonstrated that hypermethylation in the promoter region of the GAD2 gene was associated with opioid use disorder. A diagnostic model based on 10 methylation biomarkers could distinguish the opioid use disorder and healthy control groups. Several correlations between methylation levels in the GAD2 gene promoter and the duration and dosage of opioid use were observed. Transcription factors TFAP2A, Arnt and Runx1 were predicted to bind to the target sequences including several CpG sites detected in the present study in the GAD2 gene promoter. Our findings highlight and extend the role of DNA methylation in the GAD2 gene in opioid use disorder.

Plant growth stages covered the legacy effect of rotation systems on microbial community structure and function in wheat rhizosphere.

Legume-based crop rotation is conducive to improve soil multifunctionality, but how the legacy effect of previous legumes influenced the rhizosphere  microbial community of the following crops along with growth stages remains unclear. Here, the wheat rhizosphere microbial community was assessed at the regreening and filling stages with four previous legumes (mungbean, adzuki bean, soybean, and peanut), as well as cereal maize as a control. The composition and structure of both bacterial and fungal communities varied dramatically between two growth stages. The differences in fungal community structure among rotation systems were observed at both the regreening and filling stages, while the difference in bacterial community structure among rotation systems was observed only at the filling stage. The complexity and centrality of the microbial network decreased along with crop growth stages. The species associations were strengthened in legume-based rotation systems than in cereal-based rotation system at the filling stage. The abundance of KEGG orthologs (KOs) associated with carbon, nitrogen, phosphorus, and sulfur metabolism of bacterial community decreased from the regreening stage to the filling stage. However, there was no difference in the abundance of KOs among rotation systems. Together, our results showed that plant growth stages had a stronger impact than the legacy effect of rotation systems in shaping the wheat rhizosphere microbial community, and the differences among rotation systems were more obvious at the late growth stage. Such compositional, structural, and functional changes may provide predictable consequences of crop growth and soil nutrient cycling.

Efficacy and safety of Chinese herbal medicines combined with cyclophosphamide for connective tissue disease-associated interstitial lung disease: A meta-analysis of randomized controlled trials.

Objectives: To evaluate the effectiveness and safety of Chinese herbal medicines (CHMs) combined with cyclophosphamide (CTX) for connective tissue disease-associated interstitial lung disease (CTD-ILD) by performing a meta-analysis. Methods: We searched RCTs of Chinese herbal medicines therapy for connective tissue disease-associated interstitial lung disease in ten databases. Methodological quality assessment was performed by the Cochrane collaboration tool. RevMan v5.3 and Stata v14.0 software were used for performing data analysis. This study was conducted and reported following the PRISMA checklist. Results: Overall, seven RCTs with 506 participants were included for this analysis. Current data indicated that Chinese herbal medicines combined with cyclophosphamide contributed to a betterment in improving the clinical efficacy rate of connective tissue disease-associated interstitial lung disease [risk ratio (RR) = 1.21, 95% confidence interval (CI): (1.09, 1.35), p = 0.0003], tended to benefit improvement of lung function, which included VC [weighted mean difference (WMD) = 9.49, 95% CI: (5.54, 13.45), p < 0.00001], FVC [standardized mean difference (SMD) = 0.83, 95% CI: (0.36, 1.29), p = 0.0005], FEV1 [SMD = 0.54, 95% CI: (0.23, 0.86), p = 0.0008], TLC [SMD = 0.90, 95% CI: (0.68, 1.13), p < 0.00001], DLCO [SMD = 1.05, 95% CI: (0.38, 1.73), p = 0.002], and MVV [SMD = 0.83, 95% CI: (0.50, 1.17), p < 0.00001], and it also could significantly reduce the HRCT integral of lungs [SMD = -2.02, 95% CI: (-3.14, -0.91), p = 0.0004] and the level of ESR [WMD = -13.33, 95% CI: (-18.58, -8.09), p < 0.00001]. Furthermore, there was no statistical significance in the incidence of adverse events (AEs), which indicate that Chinese herbal medicines combined with cyclophosphamide is safe and does not increase adverse events compared with cyclophosphamide alone. Conclusion: Our analysis indicates that Chinese herbal medicines combined with cyclophosphamide may be a more effective strategy on the treatment of connective tissue disease-associated interstitial lung disease in the clinic. Because it included studies with relatively small sample size, the results need to be confirmed by more well-designed and large-scale RCTs. Systematic Review Registration: https://10.37766/inplasy2022.12.0010.

Efficacy of Bushen Jiangu therapy in the treatment of glucocorticoid-induced osteoporosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Bushen Jiangu (BSJG), a classic traditional Chinese medicine (TCM) therapy, is widely used for treatment of GIOP. We conducted a meta-analysis to evaluate the effectiveness and safety of BSJG therapy on the treatment of GIOP. METHODS: We searched randomized controlled trials (RCTs) of BSJG therapy for GIOP in 10 databases. Methodological quality assessment was performed by using the Cochrane collaboration tool. RevMan v5.3 and Stata v14.0 software were used for performing data analysis. This study was conducted and reported following the PRISMA checklist. RESULTS: Overall, 14 RCTs with 988 participants met the inclusion criteria. Pooled results indicated that BSJG therapy contributed to a betterment in improving the clinical efficacy rate of GIOP (risk ratio [RR] = 1.22, 95% confidence interval [CI]: 1.14, 1.30, P < .00001). The pooled results also indicated that BSJG therapy increased lumbar spine bone mineral density (LS-BMD) (weighted mean difference [WMD] = 0.21, 95% CI: 0.08, 0.33, P = .001), total hip bone mineral density (TH-BMD) (WMD = 0.16, 95% CI: 0.09, 0.24, P < .0001), and femoral neck bone mineral density (FN-BMD) (WMD = 0.07, 95% CI: 0.03, 0.10, P = .0001). Furthermore, our results indicated that BSJG therapy improved visual analogue scale (VAS) score (WMD = -0.60, 95% CI: -0.97, -0.23, P = .002), parathyroid hormone (PTH) (standardized mean difference [SMD] = -0.93, 95% CI: -1.58, -0.27, P = .006), and N-terminal propeptide of type I precollagen (PINP) (SMD = 0.69, 95% CI: 0.44, 0.95, P < .00001). In terms of safety, there was no significant difference in the adverse events (AEs) between the 2 groups (RR = 1.45, 95% CI: 0.63, 3.31, P = .38). CONCLUSION: Our analysis indicates that BSJG therapy has a valid and safe effect on the treatment of GIOP in the clinic. However, the results need to be confirmed in more well-designed and large-scale RCTs.

Tryptophan Metabolism Acts as a New Anti-Ferroptotic Pathway to Mediate Tumor Growth.

Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids-produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5-HT) and 3-hydroxyanthranilic acid (3-HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine-mediated ferroptosis inhibition. Mechanistically, both 5-HT and 3-HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5-HT via degrading 5-HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5-HT treatment. Kynureninase (KYNU), which is essential for 3-HA production, confers cells resistant to ferroptotic cell death, whereas 3-hydroxyanthranilate 3,4-dioxygenase (HAAO) significantly blocks 3-HA mediated ferroptosis inhibition by consuming 3-HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti-ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.

iORbase: A database for the prediction of the structures and functions of insect olfactory receptors.

Insect olfactory receptors (iORs) with atypical 7-transmembrane domains, unlike Chordata olfactory receptors, are not in the GPCR protein family. iORs selectively bind to volatile ligands in the environment and affect essential insect behaviors. In this study, we constructed a new platform (iORbase, https://www.iorbase.com) for the structural and functional analysis of iORs based on a combined algorithm for gene annotation and protein structure prediction. Moreover, it provides the option to calculate the binding affinities and binding residues between iORs and pheromone molecules by virtual screening of docking. Furthermore, iORbase supports the automatic structural and functional prediction of user-submitted iORs or pheromones. iORbase contains the well-analyzed results of approximately 6 000 iORs and their 3D protein structures identified from 59 insect species and 2 077 insect pheromones from the literature, as well as approximately 12 million pairs of simulated interactions between functional iORs and pheromones. We also built 4 online modules, iORPDB, iInteraction, iModelTM, and iOdorTool to easily retrieve and visualize the 3D structures and interactions. iORbase can help greatly improve the experimental efficiency and success rate, identify new insecticide targets, or develop electronic nose technology. This study will shed light on the olfactory recognition mechanism and evolutionary characteristics from the perspectives of omics and macroevolution.

A highly sensitive bio-barcode immunoassay for multi-residue detection of organophosphate pesticides based on fluorescence anti-quenching.

Balancing the risks and benefits of organophosphate pesticides (OPs) on human and environmental health relies partly on their accurate measurement. A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs (triazophos, parathion, and chlorpyrifos) in apples, turnips, cabbages, and rice. Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs. DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification. The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore. The resulting fluorescence signal enables multiplexed quantification of triazophos, parathion, and chlorpyrifos residues over the concentration range of 0.01-25, 0.01-50, and 0.1-50 ng/mL with limits of detection of 0.014, 0.011, and 0.126 ng/mL, respectively. The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%-17.6%, which correlate well with results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proposed bio-barcode immunoassay is stable, reproducible and reliable, and is able to detect low residual levels of multi-residue OPs in agricultural products.