Use of machine learning to identify key factors regulating volatilization of semi-volatile organic chemicals from soil to air.

Volatilization from soil to air is a key process driving the distribution and fate of semi-volatile organic contaminants. However, quantifying this process and the key environmental governing factors remains difficult. To address this issue, the volatilization fluxes of polybrominated diphenyl ethers (PBDEs) and organophosphate esters (OPEs) from soil were determined in 16 batch experiments orthogonally with six variables (chemical property, soil concentration, air velocity, ambient temperature, soil porosity, and soil moisture) and analyzed with machine learning methods. The results showed that gradient-boosting regression tree models satisfactorily predicted the volatilization fluxes of PBDEs (r2 = 0.82 ± 0.07) and OPEs (r2 = 0.62 ± 0.13). Permutation importance analysis showed that partitioning potential of chemicals between soil and air was the most important factor regulating the volatilization of the target compounds from soil. Temperature and soil porosity played a secondary role in controlling the migration of PBDEs and OPEs, respectively, due to higher volatilization enthalpies of PBDEs than those of OPEs and dominant adsorption of OPEs on mineral surface. The effect of soil moisture was negative and positive for the volatilization fluxes of PBDEs and OPEs, respectively. These results suggested different responses in the soil-air diffusive transport of PBDEs and OPEs to high temperature and rainstorm induced by climate change.

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH and ASK1-JNK pathway are targetable to alleviate PCOS.

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.

Amino acids downregulate SIRT4 to detoxify ammonia through the urea cycle.

Ammonia production via glutamate dehydrogenase is inhibited by SIRT4, a sirtuin that displays both amidase and non-amidase activities. The processes underlying the regulation of ammonia removal by amino acids remain unclear. Here, we report that SIRT4 acts as a decarbamylase that responds to amino acid sufficiency and regulates ammonia removal. Amino acids promote lysine 307 carbamylation (OTCCP-K307) of ornithine transcarbamylase (OTC), which activates OTC and the urea cycle. Proteomic and interactome screening identified OTC as a substrate of SIRT4. SIRT4 decarbamylates OTCCP-K307 and inactivates OTC in an NAD+-dependent manner. SIRT4 expression was transcriptionally upregulated by the amino acid insufficiency-activated GCN2-eIF2α-ATF4 axis. SIRT4 knockout in cultured cells caused higher OTCCP-K307 levels, activated OTC, elevated urea cycle intermediates and urea production via amino acid catabolism. Sirt4 ablation decreased male mouse blood ammonia levels and ameliorated CCl4-induced hepatic encephalopathy phenotypes. We reveal that SIRT4 safeguards cellular ammonia toxicity during amino acid catabolism.

Tandem mass tag (TMT)-based proteomic analysis of Cryptosporidium andersoni oocysts before and after excystation.

BACKGROUND: Cryptosporidium andersoni initiates infection by releasing sporozoites from oocysts through excystation. However, the proteins involved in excystation are unknown. Determining the proteins that participate in the excystation of C. andersoni oocysts will increase our understanding of the excystation process. METHODS: Cryptosporidium andersoni oocysts were collected and purified from the feces of naturally infected adult cows. Tandem mass tags (TMT), coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis, were used to investigate the proteomic expression profiles of C. andersoni oocysts before and after excystation. RESULTS: Proteomic analysis identified a total of 1586 proteins, of which 17 were differentially expressed proteins (DEPs) upon excystation. These included 10 upregulated and seven downregulated proteins. The 17 proteins had multiple biological functions associated with control of gene expression at the level of transcription and biosynthetic and metabolic processes. Quantitative real-time RT-PCR of eight selected genes validated the proteomic data. CONCLUSIONS: This study provides information on the protein composition of C. andersoni oocysts as well as possible excystation factors. The data may be useful in identifying genes for diagnosis, vaccine development, and immunotherapy for Cryptosporidium.

Exosomal miR-365a-5p derived from HUC-MSCs regulates osteogenesis in GIONFH through the Hippo signaling pathway.

The pathogenesis of glucocorticoid (GC)-induced osteonecrosis of the femoral head (GIONFH) is still disputed, and abnormal bone metabolism caused by GCs may be an important factor. In vitro, Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cellular proliferation, and western blotting was used to investigate osteogenesis. In vivo, we used micro-computed tomography (micro-CT), H&E staining, Masson staining, and immunohistochemistry (IHC) analysis to evaluate the impact of exosomes. In addition, the mechanism by which exosomes regulate osteogenesis through the miR-365a-5p/Hippo signaling pathway was investigated using RNA sequencing (RNA-seq), luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting. The results of western blotting verified that the relevant genes in osteogenesis, including BMP2, Sp7, and Runx2, were upregulated. RNA-seq and qPCR of the exosome and Dex-treated exosome groups showed that miR-365a-5p was upregulated in the exosome group. Furthermore, we verified that miR-365a-5p promoted osteogenesis by targeting SAV1. Additional in vivo experiments revealed that exosomes prevented GIONFH in a rat model, as shown by micro-CT scanning and histological and IHC analysis. We concluded that exosomal miR-365a-5p was effective in promoting osteogenesis and preventing the development of GIONFH via activation of the Hippo signaling pathway in rats.

Investigation of the Effects and Mechanisms of Dendrobium loddigesii Rolfe Extract on the Treatment of Gout.

OBJECTIVE: Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. METHODS: An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. RESULTS: DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (P < 0.05). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (P < 0.05), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint's synovium (P < 0.05), and the serum levels of IL-1ß, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. CONCLUSION: DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint's synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.

CT-based Morphometric Analysis of Approach of Percutaneous Transforaminal Endoscopic Lumbar Interbody Fusion.

OBJECTIVES: A radiographic study was designed to measure the relationship of the exiting nerve root and its surroundings to the corresponding intervertebral disc for percutaneous transforaminal endoscopic lumbar interbody fusion to better understand the regional anatomy and to improve clinical applications. METHODS: A retrospective study from January 2017 to October 2017 was conducted at Tianjin Hospital. CT images were obtained from patients presenting low back pain (110 patients), and analysis was performed bilaterally from L2-3 to L5 S1 . In the rotating coronal plane we analyzed: the nerve root-dural sac distance at the superior and inferior margins of the disc (Js, Ji); the nerve root-pedicle distance at the medial, middle, and lateral borders of the pedicle (Pa, Pb, Pc); the pedicle width (W); and the safe working zone, defined as a trapezoid bounded by the inferior pedicle and the exiting nerve root (S). In the transverse plane, the nerve root-articular process and the shortest distance for the nerve root-articular process joint surface were analyzed at the superior and inferior margins of the disc (Gs, Gi), respectively. The groups were analyzed using ANOVA, and paired t-tests were used to compare the left and right sides. RESULTS: From L2-3 to L5 S1 , the distance of the nerve root to the dural sac was larger at the inferior margin of the disc. From L2-3 to L5 S1 , each segment of the vertebral nerve root-pedicle distance gradually decreased from medial to lateral. From L2-3 to L5 S1 , the distance from the exiting nerve root to the middle and lateral margins of the pedicle gradually decreased, with L5 S1 being the minimum. Some significant differences were observed between the left and right sides for L4-5 and L5 S1 . The pedicle width of the vertebral body and the mean area for the safe working zone gradually increased from L2-3 to L5 S1 . In the axial plane, the shortest distance between the nerve root and articular process joint surface at the inferior margin of the disc was greater than the distance for the nerve root to the articular process at the superior margin of the disc from L2-3 to L5 S1 . There were no significant differences between the two sides. CONCLUSIONS: It is more difficult to implant a cage with a width of 10 mm above the L3-4 level. By removing part of the superior articular process, the safe working area can be expanded, and damage to the nerve or other structures can be avoided when implanting a cage.

Oculocutaneous albinism type 3 (OCA3): analysis of two novel mutations in TYRP1 gene in two Chinese patients.

Oculocutaneous albinism (OCA) is a genetic disease characterized by the reduction or deficiency of melanin in eyes, skin, and hair. OCA exhibits genetic heterogeneity. Presently, there are four types of OCA named as OCA1, OCA2, OCA3, and OCA4. OCA3 is more common in African born blacks but rarely found in other ethnic populations. Our recent genotyping of patients with OCA of Chinese descent has identified two patients who were not OCA1, OCA2, or OCA4. Examination and analysis of the TYRP1 gene identified them to be having OCA3. PCR and DNA sequencing analysis found that the mutant TYPR1 alleles were present in each of the two patients, c.780-791del/c.1067G>A (p.R356Q) and c.625G>TT (p.G209LfsX1)/c.643C>T (p.H215Y). The c.780-791del and c.1067G>A mutations have been already reported. However, the c.625G>TT and c.643C>T mutations have not been previously reported and were found to be maternal and paternal mutations, respectively. Moreover, population screening and bioinformatic analysis were carried out to determine the effects of these two mutations which revealed that both the mutation were pathogenic. Based on the similar mild phenotype of these two patients, we suggest that OCA3 might be prevalent within the Chinese population.