Search

Contents [ABSTRACT FROM AUTHOR]

Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin-specific protease 22 (USP22) as a pro-oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin-specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial-mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration-approved drug library screening and identified topotecan as a clinically applicable USP22-targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3-induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22-targeting drug to limit melanoma metastasis., Competing Interests: The authors have no relevant financial or nonfinancial interests to disclose., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Hybrid metal halide materials with charming phase transition behaviors have attracted considerable attention. In former works, much attention has been focused on the phase transition triggered by the order-disorder or displacement motions of the organic component. However, manipulating the variation of the inorganic component to achieve the phase transition has rarely been reported. Herein, two novel organic-inorganic hybrid materials, [THPM] n [AgX 2 ] n (THPM = 3,4,5,6-tetrahydropyrimidin-1-ium, X = I for 1 and Br for 2 ) with the [AgX 2 ] n n - anionic chain structure, were synthesized. At 293 K, the [AgX 2 ] n n - chains in 1 were constructed by the tetramer units of Ag atoms, while that in 2 was assembled by the dimer structure. Upon heating to 355 K, owing to the variation of the metallophilic interaction between adjacent Ag atoms, a unique transformation process from tetramer to dimer in [AgI 2 ] n n - chains of 1 can be detected and endow 1 with a giant anisotropic thermal expansion with linear strain of ∼7% and shear strain of ∼20%, which can be used as a mechanical actuator for switching. Alternatively, for 2 , no phase transition process can be observed upon the temperature variation. This work provides an effective approach to design phase transition materials triggered by the inorganic part.

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Surgery combined with radiotherapy substantially escalates the likelihood of encountering complications in early-stage cervical squamous cell carcinoma(ESCSCC). We aimed to investigate the feasibility of Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in ESCSCC and minimize the occurrence of adverse events associated with the treatment., Methods: A dataset comprising MR images was obtained from 289 patients who underwent radical hysterectomy and pelvic lymph node dissection between January 2019 and April 2022. The dataset was randomly divided into two cohorts in a 4:1 ratio.The postoperative radiotherapy options were evaluated according to the Peter/Sedlis standard. We extracted clinical features, as well as intratumoral and peritumoral radiomic features, using the least absolute shrinkage and selection operator (LASSO) regression. We constructed the Clinical Signature (Clinic&#95;Sig), Radiomics Signature (Rad&#95;Sig) and the Deep Transformer Learning Signature (DTL&#95;Sig). Additionally, we fused the Rad&#95;Sig with the DTL&#95;Sig to create the Deep Learning Radiomic Signature (DLR&#95;Sig). We evaluated the prediction performance of the models using the Area Under the Curve (AUC), calibration curve, and Decision Curve Analysis (DCA)., Results: The DLR&#95;Sig showed a high level of accuracy and predictive capability, as demonstrated by the area under the curve (AUC) of 0.98(95% CI: 0.97-0.99) for the training cohort and 0.79(95% CI: 0.67-0.90) for the test cohort. In addition, the Hosmer-Lemeshow test, which provided p-values of 0.87 for the training cohort and 0.15 for the test cohort, respectively, indicated a good fit. DeLong test showed that the predictive effectiveness of DLR&#95;Sig was significantly better than that of the Clinic&#95;Sig(P < 0.05 both the training and test cohorts). The calibration plot of DLR&#95;Sig indicated excellent consistency between the actual and predicted probabilities, while the DCA curve demonstrating greater clinical utility for predicting the pathological features for adjuvant radiotherapy., Conclusion: DLR&#95;Sig based on intratumoral and peritumoral MRI images has the potential to preoperatively predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma (ESCSCC)., (© 2024. The Author(s).)

Objective: To understand the current status of personal protection in occupational population at high risk for brucellosis in China and provide evidence for the evaluation of implementation of National Brucellosis Prevention and Control Plan (2016-2020). Methods: Four counties in Shanxi Province and Xinjiang Uygur Autonomous Region were selected to conduct a questionnaire survey in occupational population at high risk for brucellosis from December 2019 to July 2020 by using cross-sectional survey methods. Results: A total of 2 384 persons at high risk for brucellosis were surveyed, and the standardized utilization rate of personal protective equipment (PPE) was 20.13% (480/2 384). The utilization rate of glove, mask, rubber shoe, and work cloth were 38.26% (912/2 384), 31.80% (758/2 384), 32.01% (763/2 384) and 30.87% (736/2 384),respectively. There were significant differences in the utilization rate and standardized utilization rate of the four types of PPE among populations in different age, occupation, educational level and area groups (all P <0.001). The utilization rate and standardized utilization rate of PPE were lower in people over 60 years old, women, farmers, and those with lower educational level. The results of multivariate analysis showed that occupation and area were the influencing factors for the standardized utilization of PPE, the standardized utilization rates of PPE were higher in herdsmen and veterinarians. The standardized utilization rate of PPE in Yanggao County and Huocheng County was significantly higher than that in Zuoyun County and Hunyuan County. Conclusions: The utilization rate of the four types of PPE in occupational population at high risk for brucellosis was not high in China, and the standardized utilization rate was low, lower than the requirement in National Brucellosis Prevention and Control Plan, and there were significant differences among different areas. It is urgent to distribute PPE to occupational population at high risk for brucellosis and carry out health education about PPE utilization. Meanwhile, it is necessary to strengthen information exchange or sharing among different areas.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aβ 25-35- induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aβ 25-35 -injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aβ 25-35 -induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aβ 25-35 -induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aβ 25-35 -induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: We performed a meta-analysis to investigate the association of the systemic inflammation response index (SIRI) with long-term survival outcomes in patients with gastrointestinal malignancy. Methods: PubMed, Web of Science and Embase were searched for relevant studies evaluating the prognostic significance of the SIRI in gastrointestinal malignancies until May 2023. Results: 30 studies with 10,091 patients were included. The pooled results identified that patients in the high SIRI group had a worse overall survival and disease-free survival, which was observed across various tumor types, tumor stages and primary treatments. Conclusion: An elevated SIRI is negatively associated with worse survival outcomes of gastrointestinal malignancy patients and can be used as a risk stratification index for gastrointestinal malignancies.

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on β-amyloid protein 25-35(Aβ&#95;(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aβ&#95;(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of β-amyloid protein 1-42(Aβ&#95;(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aβ&#95;(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol with β-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aβ&#95;(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aβ&#95;(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aβ&#95;(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aβ&#95;(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aβ&#95;(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

Drug resistance in tumours has seriously hindered the therapeutic effect. Tumour drug resistance is divided into primary resistance and acquired resistance, and the recent study has found that a significant proportion of cancer cells can acquire stable drug resistance from scratch. This group of cells first enters the drug tolerance state (DT state) under drug pressure, and gradually acquires stable drug resistance through adaptive mutations in this state. Although the specific mechanisms underlying the formation of drug tolerant cells (DTCs) remain unclear, various proteins and signalling pathways have been identified as being involved in the formation of DTCs. In the current review, we summarize the characteristics, molecular mechanisms and therapeutic strategies of DTCs in detail., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Liu, Chen, Cao, Chu, Lin, Wang and Wu.)

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative to canonical FSH. KN015 supports the in vitro development of mouse follicles from primary to preovulatory stage with higher efficiency than canonical FSH and enhanced post-fertilization development rates of the ovulated oocytes. The use of KN015 also allows us to compare the dynamic transcriptome changes in oocytes and granulosa cells at different stages, in vivo and in vitro. In particular, KN015 facilitates mRNA accumulation in growing mouse oocytes and prevents spontaneous luteinization of granulosa cells in vitro. Novel analyses of transcriptome changes in this study reveal that the in vivo oocytes were more efficient than in vitro oocytes in terms of maternal mRNA clearing during meiotic maturation. KN015 promotes the degradation of maternal mRNA during in vitro oocyte maturation, improves cytoplasmic maturation and, therefore, enhances embryonic developmental potential. These findings establish new transcriptome data for oocyte and granulosa cells at the key stages of follicle development, and should help to widen the use of KN015 as a valid and commercially available hormonal support enabling optimized in vitro development of follicles and oocytes., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ubiquitin is a small protein that can be added onto target protein for inducing target degradation, thereby modulating the activity and stability of protein. Relatively, deubiquitinases (DUBs), a class catalase that can remove ubiquitin from substrate protein, provide a positive regulation of the protein amount at transcription level, post-translational modification, protein interaction, etc. The reversible and dynamic ubiquitination-deubiquitination process plays an essential role in maintaining protein homeostasis, which is critical to almost all the biological processes. Therefore, the metabolic dysregulation of deubiquitinases often lead to serious consequences, including the growth and metastasis of tumors. Accordingly, deubiquitinases can be served as key drug targets for the treatment of tumors. The small molecule inhibitors targeting deubiquitinases has become one of the hot spots of anti-tumor drug research areas. This review concentrated on the function and mechanism of deubiquitinase system in the proliferation, apoptosis, metastasis and autophagy of tumor cells. The research status of small molecule inhibitors of specific deubiquitinases in tumor treatment is introduced, aiming to provide reference for the development of clinical targeted drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Wang, Liu, Chen, Cao, Chu, Lin, Liu and Wu.)

Leukemia inhibitory factor (LIF) is an important growth factor that supports the culture and maintenance of spermatogonial stem cells (SSCs) by suppressing spontaneous differentiation. Different LIF sequences may lead to differences in function. The protein sequences of buffalo LIF and mouse LIF differed by 65.5% according to MEGA software analysis. The PB-LIF-GFP-Puro vector was constructed, and the CHO-K1 cell line was established. The final LIF protein concentration in the CHO-K1 cell culture medium was approximately 4.268 ng/mL. Here, we report that buffalo LIF effectively maintains the self-renewal of buffalo spermatogonia during culture. Buffalo spermatogonia were cultured in conditioned medium containing no LIF (0 ng/mL), mouse LIF (1 ng/mL), mouse LIF (10 ng/mL), or buffalo LIF (1 ng/mL). Furthermore, the effects of mouse LIF and buffalo LIF culture on the maintenance of buffalo spermatogonia were determined by analyzing cell colony formation, quantitative real-time polymerase chain reaction, cell immunofluorescence, and cell counting. The buffalo LIF (1 ng/mL) group showed similar maintenance of the proliferation of buffalo spermatogonia to that in the mouse LIF (10 ng/mL) group. These results demonstrated that the proliferation of buffalo spermatogonia can be maintained in vitro by adding a low dose of buffalo LIF. This study provides a foundation for the further optimization of in vitro buffalo SSC culture systems., (© 2023 International Federation for Cell Biology.)

Two series of lanthanoid (Ln)-containing polyoxometalates (POMs) {[Ln 6 (ampH) 4 (H 2 O) 24- n (ampH 2 ) n (PW 11 O 39 ) 2 ]·21H 2 O (Ln = Tb, n = 0 ( 1 ), Ln = Er, n = 1 ( 2 )) and K 2 [Ln 6 (ampH) 4 (H 2 O) 22 (SiW 11 O 39 ) 2 ]·23H 2 O (Ln = Tb ( 3 ), Er ( 4 )) (ampH 2 = (aminomethyl) phosphonic acid)} have been synthesized with tri-lacunary Keggin-type POMs containing different types of heteroatoms. Compounds 1 and 2 display neutral organic-inorganic hybrid POM molecules containing {Ln 6 (ampH) 4 } ({Ln 6 }) cores sandwiched by two {PW 11 O 39 } units. By changing the heteroatoms from P V to Si IV , the extended 2D networks of 3 and 4 were successfully isolated where the adjacent {Ln 6 } clusters were connected by {SiW 11 O 39 } moieties. Luminescence performances and magnetic properties of 1-4 have been systematically surveyed. The solid-state fluorescence spectra of 1-4 display characteristic emissions of Ln components resulting from the 4f-4f transitions, and energy transfer from the POM segments to Ln 3+ centers in 1 and 3 has been observed based on the lifetime decay behaviors. Furthermore, all compounds can be utilized as electrocatalysts toward reduction of nitrite with high stability.

Objective: Due to inconsistency in neoadjuvant chemotherapy (NACT) response in advanced gastric cancer (GC), the indications remain the source of controversy. This study focused on identifying factors related to NACT chemosensitivity and providing the best treatment for GC cases., Methods: Clinical data in 867 GC cases treated with neoadjuvant chemotherapy were downloaded from two medical centers between January 2014 and December 2020, and analyzed by logistic regression and the least absolute shrinkage and selection operator (LASSO) for identifying potential factors that predicted NACT response and might be incorporated in constructing the prediction nomogram., Results: After the inclusion and exclusion criteria were applied, totally 460 cases were enrolled, among which, 307 were males (66.74%) whereas 153 were females (33.26%), with the age of 24-77 (average, 59.37 ± 10.60) years. Consistent with RECIST standard, 242 patients were classified into effective group (PR or CR) while 218 were into ineffective group (PD or SD), with the effective rate of 52.61%. In training set, LASSO and logistic regression analysis showed that five risk factors were significantly associated with NACT effectiveness, including tumor location, Smoking history, T and N stages, and differentiation. In terms of our prediction model, its C-index was 0.842. Moreover, calibration curve showed that the model-predicted results were in good consistence with actual results. Validation based on internal and external validation sets exhibited consistency between training set results and ours., Conclusions: This study identified five risk factors which were significantly associated with NACT response, including smoking history, clinical T stage, clinical N stage, tumor location and differentiation. The prediction model that exhibited satisfying ability to predict NACT effectiveness was constructed, which may be adopted for identifying the best therapeutic strategy for advanced GC by gastrointestinal surgeons., (© 2023. The Author(s).)

Background: The pan-immune-inflammation value (PIV) has been reported as a novel prognostic biomarker in multiple malignancies. The aim of this study is to investigate the prognostic value of the PIV in patients with colorectal cancer., Methods: We comprehensively searched electronic databases including PubMed, Embase and Web of Science up to August 2022. The endpoints were survival outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) for survival data were collected for analysis., Results: Six studies including 1879 participants were included. A significant heterogeneity in the PIV cut-off value among studies was observed. The combined results indicated that patients in the high baseline PIV group had a worse overall survival (HR=2.09; 95%CI: 1.67-2.61; P<0.0001; I 2 = 7%) and progression-free survival (HR=1.82; 95%CI: 1.49-2.22; P<0.0001; I 2 = 15%). In addition, early PIV increase after treatment initiation was significantly associated with decreased overall survival (HR=1.79; 95%CI: 1.13-2.93; P=0.01; I 2 = 26%), and a trend toward poor progression-free survival (HR=2.00; 95%CI: 0.90-4.41; P=0.09; I 2 = 70%)., Conclusion: Based on existing evidence, the PIV could act as a valuable prognostic index in patients with colorectal cancer. However, the heterogeneity in the PIV cut-off value among studies should be considered when interpreting these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Liu, Liu, Tong, Liang and Chen.)

Since the water oxidation half-reaction requires the transfer of multi-electrons and the formation of O-O bond, it's crucial to investigate the catalytic behaviours of semiconductor photoanodes. In this work, a bio-inspired copper-bipyridine catalyst of Cu(dcbpy) is decorated on the nanoporous Si photoanode (black Si, b-Si). Under AM1.5G illumination, the b-Si/Cu(dcbpy) photoanode exhibits a high photocurrent density of 6.31 mA cm -2 at 1.5 V RHE at pH 11.0, which is dramatically improved from the b-Si photoanode (1.03 mA cm -2 ) and f-Si photoanode (0.0087 mA cm -2 ). Mechanism studies demonstrate that b-Si/Cu(dcbpy) has improved light-harvesting, interfacial charge-transfer, and surface area for water splitting. More interestingly, b-Si/Cu(dcbpy) exhibits a pH-dependent water oxidation behaviour with a minimum Tafel slope of 241 mV/dec and the lowest overpotential of 0.19 V at pH 11.0, which is due to the monomer/dimer equilibrium of copper catalyst. At pH ∼11, the formation of dimeric hydroxyl-complex could form O-O bond through a redox isomerization (RI) mechanism, which decreases the required potential for water oxidation. This in-depth understanding of pH-dependent water oxidation catalyst brings insights into the design of dimer water oxidation catalysts and efficient photoanodes for solar energy conversion., (© 2022 Wiley-VCH GmbH.)

Here, we realize a regulable cross-coupling reaction using alcohols as alkylating reagents to functionalize benzothiazoles. Two types of cross-coupling products are obtained with the highest isolated yields of up to 99% and 90% for alkyl- and acetyl-derived benzothiazoles, respectively, which opens up a broad research prospect for expanding alcohols as alkylating reagents.

The purpose of this study was to evaluate the predictive value of ultrasound markers measured at different time points of the controlled ovarian hyperstimulation (COH) cycle on ovarian response and outcome indicators in the IVF-ET cycle. According to the oestrogen level and the number of retrieved oocytes, patients who planned for COH treatment were separated into low-response group, normal and high-response group. The ovarian stromal artery flow parameters on the day of pituitary down-regulation, day 1, day 7, day 10, and the day of hCG injection were collected prospectively. We also have collected the data of cumulus oophorus count on the day of hCG injection by transvaginal sonography. Compared with the low-response group, on the first day of the COH cycle PI, RI, and S/D were lower in the high-response group than they were in the low-response group ( p  < .05). PSV and EDV were significantly higher in the high-response group than they were in the low-response group ( p  < .01), and the PSV on the first day of the COH cycle have statistical significance in predicting the number of high-quality embryos. The number of cumulus oophorus on the day of hCG injection has statistical significance in predicting the number of oocytes retrieved and fertilised oocytes. We conclude that the ovarian stromal artery flow parameters on the first day of the COH cycle and cumulus oophorus count on hCG injection day can serve as efficient indicators for an early assessment of ovarian response and individualised ovulation induction.IMPACT STATEMENT What is already known on this subject? AMH, AFC, and the age of the patient are well-known effective parameters for the evaluation of ovarian response, but these are insufficient and full of individual differences. Some researchers have investigated the value of colour Doppler ultrasound and cumulus oophorus in assessing ovarian response, but no definitive conclusion has been reached. What do the results of this study add? The hemodynamic parameters of ovarian stromal artery on the first day of the COH cycle and the number of cumulus oophorus on the day of hCG injection detected by Transvaginal Colour Doppler Sonography (TV-CDS) could be used to predict the ovarian response. What are the implications of these findings for clinical practice and/or further research? Ovarian stromal artery flow parameters and cumulus oophorus detected by TV-CDS can potentially be offered as a complementary parameter for ovarian reserve.

In this work, we report two supramolecular isomorphic dodecanuclear cobalt complexes, [Co 12 ( mtz ) 3 (L) 6 (NO 3 ) 2 (OH)(N 3 ) 3 ]·(OH) 3 (1) and [Co 12 ( mtz ) 3 (L) 6 (NO 3 ) 2 (OH)(N 3 )(OAc)]·(OH) 4 (2), (H mtz = 5-methyl-1 H -tetrazole, H 2 L = 7,7'-(ethane-1,1-diyl) diquinolin-8-ol) crystallizing in the P̄ space group with the same unit cell parameters. In 1 and 2, two pirate hat-like hexanuclear Co 6 (NO 3 )(L) 3 units form the same dodecanuclear metal shell, but the ligands between the hexanuclear units as the core are distinct. The introduction of acetate anions leads to a blue shift of the absorption band in the visible region. Magnetism studies indicate an antiferromagnetic interaction between the Co II ions in the clusters.

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases., (© 2022. The Author(s).)

Background: In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer., Methods: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed from the inception to January 2021 for all studies comparing ICGFL with non-ICGFL in GC patients undergoing minimal access gastrectomy. The primary outcome was the total number of harvested lymph nodes. The secondary endpoints were the number of metastatic LNs, operative time, estimated blood loss, and postoperative complications. The registration number of this protocol is PROSPERO CRD42020203443., Results: A total of 13 studies including 1882 participants were included. In this meta-analysis, the use of ICGFL was associated with a higher number of harvested LNs (40.33 vs. 33.40; MD = 6.93; 95%CI: 4.28 to 9.58; P < 0.0001; I 2  = 86%). No significant difference was found between the ICGFL and control groups in terms of metastatic LNs (2.63 vs. 2.42; MD = 0.21; 95%CI: -0.46 to 0.87; P = 0.54; I 2  = 0%). In addition, the use of ICGFL could be safely performed without increasing the operative time (P = 0.49), estimated blood loss (P = 0.26) and postoperative complications (P = 0.54)., Conclusion: The use of ICGFL may be a useful tool facilitating complete lymph node dissection during minimally invasive GC resection. However, more high-quality RCTs with large sample size are needed to validate this issue., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The present study aimed to investigate the application safety of bivalirudin combined with ticagrelor in the emergency percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: From October 1, 2018, to December 30, 2019, 210 patients with STEMI admitted to the Department of Cardiology who underwent emergency PCI were randomly divided into the bivalirudin group (group A, N = 105) and the unfractionated heparin group (group B, N = 105). Before the emergency PCI operation after admission, the loading dose of aspirin (300 mg) was given orally, and then 100 mg/d. At the same time, the loading dose of ticagrelor (180 mg) was administered orally, and then 90 mg/bid. The adverse events and the hemorrhage events 30 days after the operation were observed and recorded., Results: There were five hemorrhage cases in the bivalirudin group, with one case of secondary hemorrhage and four cases of mild hemorrhage. There were 14 hemorrhages in the unfractionated heparin group with one case of secondary hemorrhage and thirteen cases of mild hemorrhage. In terms of mild hemorrhage, the hemorrhage rate in the bivalirudin group was significantly lower than that in the unfractionated heparin group (3.8% vs. 12.4%, P = 0.040). One patient died in the unfractionated heparin group, while no deaths occurred in the bivalirudin group during the thirty days of follow-up. No myocardial infarction, revascularization, or stroke occurred in the two groups within 30 days after the operation., Conclusion: Compared with unfractionated heparin combined with ticagrelor in patients with STEMI undergoing emergency PCI treatment, bivalirudin combined with ticagrelor could significantly reduce the occurrence of mild hemorrhage events, and it would not increase the incidence of MACE during the 30 days of follow-up.

Antibiotics produced by soil microorganisms have been widespread and have cured the most prevalent diseases since 1940s. However, recent bacterial resistance to existing antibacterial drugs is causing a public health crisis. The structure-activity relationship of antibiotics needs to be established to search for existing antibiotics-based next-generation drug candidates that can conquer the challenge of bacterial resistance preparedness, which relies on the development of highly efficient total synthesis strategies. The solid-phase strategy has become important to circumvent tedious intermediate isolation and purification procedures with simple filtrations. This review will give a brief overview of recent applications of solid-phase strategy in the total synthesis of antibiotics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Computed tomography (CT) is the current gold standard for the detection of pulmonary nodules but has high radiation burden. In contrast, many radiologists tried to use magnetic resonance imaging (MRI) to replace CT because MRI has no radiation burden associated. Due to the lack of high-level evidence of comparison of the diagnostic accuracy of MRI versus CT for detecting pulmonary nodules, it is unknown whether CT can be replaced successfully by MRI. Therefore, the aim of this study was to compare the diagnostic accuracy of MRI versus CT for detecting pulmonary nodules., Methods: Electronic databases PubMed, EmBase, and Cochrane Library were systematically searched from their inception to September 2017 to identify studies in which CT/MRI was used to diagnose pulmonary nodules. According to true positive, true negative, false negative, and false positive extracted from the included studies, we calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) using Stata version 14.0 software (STATA Corp, TX)., Results: A total of 8 studies involving a total of 653 individuals were included. The pooled sensitivity, specificity, PLR, NLR, and AUC were 0.91 (95% confidence interval [CI]: 0.80-0.96), 0.76 (95%CI: 0.58-0.87), 3.72 (95%CI: 2.05-6.76), 0.12 (95%CI: 0.06-0.27), and 0.91 (95%CI: 0.88-0.93) for MRI respectively, while the pooled sensitivity, specificity, PLR, NLR, and AUC for CT were 1.00 (95%CI: 0.95-1.00), 0.99 (95%CI: 0.78-1.00), 79.35 (95%CI: 3.68-1711.06), 0.00 (95%CI: 0.00-0.06), and 1.00 (95%CI: 0.99-1.00), respectively. Further, we compared the diagnostic accuracy of CT versus MRI and found that compared with MRI, CT shows statistically higher sensitivity (odds ratio [OR] for MRI vs CT: 0.91; 95%CI: 0.85-0.98; P value .010), specificity (OR: 0.82; 95%CI: 0.69-0.97; P value .019), PLR (OR: 0.29; 95%CI: 0.10-0.83; P value 0.02), AUC (OR: 0.91; 95%CI: 0.89-0.94; P value < .001), and lower NLR (OR: 8.72; 95%CI: 1.57-48.56; P value .013)., Conclusion: Our study suggested both CT and MRI have a high diagnostic accuracy in diagnosing pulmonary nodules, while CT was superior to MRI in sensitivity, specificity, PLR, NLR, and AUC, indicating that in terms of the currently available evidence, MRI could not replace CT in diagnosing pulmonary nodules., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: We retrospectively analyzed the distribution of distant lymph node metastasis and its impact on prognosis in patients with metastatic NPC after treatment., Methods: From 2010 to 2016, 219 NPC patients out of 1,601 (182 from the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, and 37 from the Affiliated Dongguan Hospital, Southern Medical University) developed distant metastasis after primary radiation therapy. Metastatic lesions were divided into groups according to location: bones above the diaphragm (supraphrenic bone, SUP-B); bones below the diaphragm (subphrenic bone, SUB-B); distant lymph nodes above the diaphragm (supraphrenic distant lymph nodes, SUP-DLN); distant lymph nodes below the diaphragm (subphrenic distant lymph nodes, SUB-DLN), liver, lung, and other lesions beyond bone/lung/distant lymph node above the diaphragm (supraphrenic other lesions, SUP-OL); other lesions beyond bone/liver/distant lymph node below the diaphragm (subphrenic other lesions, SUB-OL); the subtotal above the diaphragm (supraphrenic total lesions, SUP-TL); and the subtotal below the diaphragm (subphrenic total lesions, SUB-TL). Kaplan-Meier methods were used to estimate the probability of patients' overall survival (OS). Univariate and multivariate analyses were applied using the Cox proportional hazard model to explore prediction factors of OS., Results: The most frequent metastatic locations were bone (45.2%), lung (40.6%), liver (32.0%), and distant lymph nodes (20.1%). The total number of distant lymph node metastasis was 44, of which 22 (10.0%) were above the diaphragm, 18 (8.2%) were below the diaphragm, and 4 (1.8%) were both above and below the diaphragm. Age (HR: 1.02, 95% CI: 1.00, 1.03, p = 0.012), N stage (HR: 1.26, 95% CI: 1.04, 1.54, p = 0.019), number of metastatic locations (HR: 1.39, 95% CI: 1.12, 1.73, p = 0.003), bone (HR: 1.65, 95% CI: 1.20, 2.25, p = 0.002), SUB-B (HR: 1.51, 95% CI: 1.07, 2.12, p = 0.019), SUB-DLN (HR: 1.72, 95% CI: 1.03, 2.86, p = 0.038), and SUB-O L(HR: 4.46, 95% CI: 1.39, 14.3, p = 0.012) were associated with OS. Multivariate analyses revealed that a higher N stage (HR: 1.23, 95% CI: 1.00, 1.50, p = 0.048), SUB-DLN (HR: 1.72, 95% CI: 1.02, 2.90, p = 0.043), and SUB-OL (HR: 3.72, 95% CI: 1.14, 12.16, p = 0.029) were associated with worse OS., Conclusion: Subphrenic lymph node metastasis predicts poorer prognosis for NPC patients with metachronous metastasis; however, this needs validation by large prospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Zhang, Liang, Chen, Zhi, Yin, Wang, Dong and Chen.)

In this study, we used genotyping by sequencing (GBS) to examine the genetic diversity of 22 strains of Lingzhi and the quality differences in 15 fruit bodies of Lingzhi from different Chinese regions. The phylogenetic trees of 22 strains were constructed based on ITS (Internal transcribed spacer) and SNP (single nucleotide polymorphism). Moisture, ash, water-soluble extracts, alcohol-soluble extracts, polysaccharides, and triterpenoids from 15 fruit bodies of Lingzhi were detected and analyzed based on Chinese Pharmacopoeia and the US Pharmacopoeia references. Moreover, the monosaccharide composition of polysaccharides was studied using PMP-HPLC, and the effect of polysaccharides on the proliferation rate of splenocytes was investigated in vitro. The identification results of these strains by the phylogenetic trees which were constructed based on ITS sequences and SNPs showed that most of the strains applied in the main producing areas of Lingzhi in China were accurate except for a few inaccurate strains. The moisture, ash, water and alcohol soluble extractive, polysaccharide and triterpenoid content of all samples were meet the requirements of the Chinese Pharmacopoeia, while the polysaccharide and triterpenoid content of less than half of the samples meet the requirements of the U.S. Pharmacopoeia. The polysaccharide extracted from these samples have different effects on the proliferation rate of spleen cells. To sum up, this is the first study that reported on the differences in Lingzhi strains from the main producing areas in China. The quality of some fruit bodies did not meet the pharmacopeia requirements, and wrong strains were used in some production areas; thus, strains should be given special attention before legal processing., (© 2021. The Author(s).)

The interest in indole dearomatization, which serves as a useful tool in the total synthesis of related alkaloid natural products, has recently been renewed with the intention of developing new methods efficient in both yield and stereoselective control. Here, we report an enzymatic approach for the oxidative dearomatization of indoles in the asymmetric synthesis of a variety of furoindolines with a vicinal quaternary carbon stereogenic center. This approach depends on the activity of a flavin-dependent monooxygenase, TsrE, which is involved in the biosynthesis of bicyclic thiopeptide antibiotic thiostrepton. TsrE catalyzes 2,3-epoxidation and subsequent epoxide opening in a highly enantioselective manner during the conversion of 2-methyl-indole-3-acetic acid or 2-methyl-tryptophol to furoindoline, with up to >99 % conversion and >99 % ee under mild reaction conditions. Complementing current chemical methods for oxidative indole dearomatization, the TsrE activity-based approach enriches the toolbox in the asymmetric synthesis of products possessing a furoindoline skeleton., (© 2021 Wiley-VCH GmbH.)

The microenvironment in the seminiferous tubules of buffalo changes with age, which affects the self-renewal and growth of spermatogonial stem cells (SSCs) and the process of spermatogenesis, but the mechanism remains to be elucidated. RNA-seq was performed to compare the transcript profiles of pre-pubertal buffalo (PUB) and adult buffalo (ADU) seminiferous tubules. In total, 17,299 genes from PUB and ADU seminiferous tubules identified through RNA-seq, among which 12,271 were expressed in PUB and ADU seminiferous tubules, 4,027 were expressed in only ADU seminiferous tubules, and 956 were expressed in only PUB seminiferous tubules. Of the 17,299 genes, we identified 13,714 genes that had significant differences in expression levels between PUB and ADU through GO enrichment analysis. Among these genes, 5,342 were significantly upregulated and possibly related to the formation or identity of the surface antigen on SSCs during self-renewal; 7,832 genes were significantly downregulated, indicating that genes in PUB seminiferous tubules do not participate in the biological processes of sperm differentiation or formation in this phase compared with those in ADU seminiferous tubules. Subsequently, through the combination with KEGG analysis, we detected enrichment in a number of genes related to the development of spermatogonial stem cells, providing a reference for study of the development mechanism of buffalo spermatogonial stem cells in the future. In conclusion, our data provide detailed information on the mRNA transcriptomes in PUB and ADU seminiferous tubules, revealing the crucial factors involved in maintaining the microenvironment and providing a reference for further in vitro cultivation of SSCs., (© 2021 Wiley-VCH GmbH.)

Aim: To identify the risk factors of epiphora in patients with anatomical patency after surgical repair of canalicular laceration., Methods: This retrospective case series included 178 cases of canalicular laceration repair from 2005 to 2012. Demographic data collected from each patient included age, sex, type of injury, distance from the distal lacerated end of the canaliculus to the punctum, the severity score for the structural abnormity of the medial canthus, the duration of stent placement, and the timing of surgery. The risk factors for epiphora were evaluated using Logistic regression models., Results: Among the 178 cases, 45 (25.3%) with lacrimal patency after irrigation had symptomatic epiphora at the final follow-up. Patients' sex, age, type of injury, duration of stent placement, timing of surgery, and concurrent trauma were not found to be significantly associated with symptomatic epiphora after surgical repair of the lacerated canaliculus ( P >0.05). A distance of more than 5 mm from the distal cut end to the punctum was closely and significantly associated with symptomatic epiphora after surgical repair of the lacerated canaliculus ( P <0.01). Symptomatic epiphora was significantly more frequent in patients with higher severity scores for structural abnormities of the medial canthus ( P <0.01)., Conclusion: Our results indicate that the risk factors for postoperative symptomatic epiphora include a further distance between the distal cut end and the lacrimal punctum and a higher severity score for structural abnormities of the medial canthus. These findings could be used to prognosticate postoperative symptomatic epiphora., (International Journal of Ophthalmology Press.)

Objective: The aim of the present study was to evaluate the effectiveness and safety of nicorandil in improving the area of myocardial infarction in patients with acute myocardial infarction (AMI)., Methods: One hundred and twenty patients with acute ST-segment elevation myocardial infarction (STEMI) admitted to our hospital between December 1, 2018 and December 31, 2019 were selected and randomly allocated to the experimental group (group A, n = 60) and the control group (group B, n = 60). In the experimental group, an infusion of nicorandil was given intravenously before the first balloon dilation or 1 minute before the stent placement, and with the completion of the infusion, nicorandil maintenance infusion was given. In the control group, only balloon dilation and stent placement were undertaken., Results: The postoperative peak levels of myoglobin, creatine kinase isoform and hypersensitive troponin T were significantly lower in group A than in group B (p < 0.05). Moreover, the left ventricular ejection fraction (LVEF) on the 180th day post operation was substantially greater in group A than in group B (p < 0.01), and the area of myocardial infarction was significantly smaller in patients in group A than those in group B on the 180th day post operation (p < 0.01). In terms of the safety, there were no statistically significant differences in the incidence of slow flow/no reflow, malignant arrhythmias, and hypotension within 24 hours post operation between the two groups (p > 0.05), and no major adverse cardiovascular event (MACE) occurred in either group during the postoperative follow-up period of 180 days (p > 0.05)., Conclusion: Intravenous administration of nicorandil in patients with STEMI during the perioperative percutaneous coronary intervention (PCI) period was effective in reducing the area of myocardial infarction and myocardial injury without increasing the incidence of malignant arrhythmias, hypotension, or composite cardiovascular events during the drug administration period.

Introduction: Associations of variations in PLA2R1 and HLA-DQA1 genes with susceptibility to idiopathic membranous nephropathy (IMN) have been well documented. Association with spontaneous remission, however, is poorly defined in the Chinese Han population., Methods: A Chinese cohort of 117 IMN patients and 138 healthy controls were recruited between July 2009 and November 2019. Case-control studies for single-nucleotide polymorphisms (SNPs) within HLA-DQA1 (rs2187668) and PLA2R1 (rs35771982, rs4664308, rs3749117, rs3749119) genes were performed. The contributions of these polymorphisms to predict susceptibility, titre of autoantibodies against the M-type phospholipase A2 receptor (anti-PLA2R1), glomerular PLA2R1 expression, and spontaneous remission were analysed., Results: We found that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) were strongly associated with IMN susceptibility, while SNP (rs2187668) within HLA-DQA1 did not increase the risk of IMN. All SNPs in PLA2R1 and HLA-DQA1 were not statistically associated with anti-PLA2R1 titre, glomerular PLA2R1 expression and spontaneous remission after Bonferroni correction ( P >0.0167). Clinical and pathological parameters such as lower levels of serum albumin, higher levels of anti-PLA2R1 and glomerular PLA2R1 expression were independent risk factors for non-spontaneous remission., Conclusion: This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN.

Ferulic acid (FA) has potential therapeutic effects in multiple diseases including cardiovascular diseases. However, the effect and molecular basis of FA in heart failure (HF) has not been thoroughly elucidated. Herein, we investigated the roles and mechanisms of FA in HF in isoproterenol (ISO)-induced HF rat model. Results found that FA ameliorated cardiac dysfunction, alleviated oxidative stress, reduced cell/myocardium injury-related enzyme plasma level, inhibited cardiocyte apoptosis in ISO-induced HF rat models. Moreover, FA reduced the co-localization of Keap1 and nuclear factor-E2-related factor 2 (Nrf2) in heart tissues of ISO-induced HF rats, and FA alleviated the inhibitory effects of ISO on expressions of p-Nrf2, heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1). Additionally, Nrf2 signaling pathway inhibitor ML385 showed adverse effects. FA weakened the effects of ML385 in ISO-induced HF rat models. Collectively, FA ameliorated HF by decreasing oxidative stress and inhibiting cardiocyte apoptosis via activating Nrf2 pathway in ISO-induced HF rats. Our data elucidated the underling molecular mechanism and provided a novel insight into the cardioprotective function of FA, thus suggested the therapeutic potential of FA in HF treatment.

Objective: To study the structure and function of human sperm mitochondria before and after the freezing-thawing process., Methods: Human sperm from healthy donors were subjected to the slow freezing-thawing process, and the sperm mitochondrion-related indexes compared before and after cryopreservation. The ultrastructural changes of the mitochondria were observed under the projection electron microscope, the mitochondrial membrane potential (MMP) and seminal adenosine triphosphate (ATP) content measured by immunofluorescence labeling and ELISA, respectively, and the sperm oxidative stress related indexes detected before and after sperm cryopreservation., Results: Electron microscopy showed loose structures and widened crests of the sperm mitochondria, some with vacuole-like changes after the freezing-thawing process. The sperm after cryopreservation, compared with those before it, exhibited significantly increased contents of oxygen free radicals (［11.6 ± 3.8］% vs ［9.6 ± 4.1］%, P < 0.05) and malondialdehyde (［3.2 ± 1.4］ vs ［2.3 ± 1.2］ nmol/108, P < 0.05), but decreased antioxidant capacity (［0.6 ± 0.4］ vs ［0.9 ± 0.4］ nmol/108, P < 0.05), superoxide dismutase activity (［0.9 ± 0.4］ vs ［9.1 ± 3.9］ nmol/108, P < 0.05), MMP (［52.2 ± 6.2］% vs ［55.7 ± 4.9］%, P = 0.026) and ATP production (［56.5 ± 9.0］ vs ［61.3 ± 10.4］ pmol/106, P = 0.014)., Conclusions: The freezing-thawing process can cause ultrastructural disorder of human sperm mitochondria, reduce their membrane potential and decrease their ATP production.

The photocycloaddition reaction of benzene with alkenes has become a significant approach for organic chemists and thus has been frequently utilized as a key step in the total synthesis of natural products. In this mini-review, the recent developments in [4 + 2] and [2 + 2] photocycloaddition reactions will be emphasized in constructing core scaffolds of complex natural products. By combining them together, we aim to demonstrate the utility and reinstate the importance of this methodology.

Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD., (© 2020 The Author(s).)

Protein ubiquitination, a major and conserved post-translational modification, is known to play a critical regulatory role in many biological processes in eukaryotes. Although several ubiquitinated proteins have been found in buffalo (Bubalus bubalis) testis in our previous studies, large-scale profiling of buffalo testis ubiquitome has not been reported to date. In the present study, we first identified a global profiling of lysine ubiquitination of adult buffalo testis using a highly sensitive LC-MS/MS coupled with immune-affinity enrichment of ubiquitinated peptides. In total, 422 lysine ubiquitination sites were identified in 262 proteins in adult buffalo testis tissue. Bioinformatics analysis showed that the ubiquitinated proteins are involved in a variety of biological processes and diverse subcellular localizations. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein interaction network analysis indicated that proteasome, glycolysis/gluconeogenesis and gap junction pathways are modulated by protein ubiquitination in testis. Besides, 44 ubiquitinated proteins may involve in spermatogenesis according to the SpermatogenesisOnline database, of which, the ubiquitination of HSPA2 and UCHL1 were confirmed by Immunoprecipitation (IP)/Western blot analysis. Taken together, these data provide a global view of ubiquitome in buffalo testis for the first time, and serve as an important resource for exploring the physiological role especially spermatogenesis of lysine ubiquitination in testis in mammals., (© 2020 The Author(s).)

The water buffalo is an important dual-purpose livestock that is widespread throughout central and southern China. However, there has been no characterization of the population genetics of Chinese buffalo. Using an Axiom buffalo genotyping array (Thermo Fisher Scientific, Wilmington, DE), we analyzed the genetic diversity, linkage disequilibrium pattern, and signature of selection in 176 Chinese buffaloes from 13 breeds. A total of 35,547 SNP passed quality control and were used for further analyses. Population genetic analysis revealed a clear separation between swamp and river types. Ten Chinese indigenous breeds were clustered into the swamp group, the Murrah and Nili-Ravi breeds were clustered into the river group, and the crossbred breed was closer to the river group. Genetic diversity analysis showed that the swamp group had a lower average expected heterozygosity. Linkage disequilibrium decay distance was much shorter in the swamp group compared with the river group, with an average square of correlation coefficient value of 0.2 of approximately 50 kb. Analysis of runs of homozygosity indicated extensive remote and recent inbreeding within swamp and river groups, respectively. Moreover, one genomic region under selection was detected between the river and swamp groups. Our findings contribute to our understanding of the characterization of population genetics in Chinese buffaloes, which in turn may be used in buffalo breeding programs., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Chromophoric dissolved organic matter (CDOM) optical absorption characteristics, CDOM spectral slopes ( S 275-295 ), contribution of each component to water absorption, and the effects of environmental factors on them were analyzed to determine the sources and composition of CDOM in high-turbidity waters on the Loess Plateau. Samples in rivers and lakes (saline and freshwater) in the Loess Plateau area of Shaanxi and Inner Mongolia were collected in May 2018. The results demonstrated significant differences in CDOM absorption optical characteristics between rivers and lakes. The average a CDOM (440) (CDOM concentration, 8.45 m -1 ) in lakes was higher than that of rivers (2.70 m -1 ), and the saline lakes showed a higher CDOM concentration (13.52 m -1 ) than the freshwater lakes (3.38 m -1 ). Moreover, the light utilization efficiency of freshwater lakes is higher than that of saline lakes and turbid rivers. Great differences in pH and dissolved organic carbon (DOC) were observed between different types of water ( P <0.01). The differences in electrical conductivity (EC), turbidity (Tur), and total suspended matter concentration (TSM) were significant with no statistical significances ( P >0.1). The chlorophyll a concentration (Chla) in saline lakes was close to the Chla concentration in freshwater lakes if extreme values were excluded. In addition, the CDOM molecular weights of lake water were lower than those in the rivers, while CDOM molecular weights in saline lakes were lower than those in freshwater lakes based on the S 275-295 . Analyses of specific ultraviolet absorbance (SUVA 254 ) were also conducted to determine the sources of CDOM in different water types, and the results showed that the more terrigenous humus were brought into the rivers and saline lakes compared with the freshwater lakes. Redundancy analysis (RDA) indicated that river and lake water quality parameters of the cumulative variance explained rates were 35.2% for river samples and 61.4% for lake samples, and 100% for samples in the saline and freshwater lakes individually. The results of RDA showed that dissolved oxygen (DO), water temperature, and EC exerted significant effects on CDOM optical properties of the river ( P <0.01), while DOC, TSM, and Tur had a great influence on the CDOM optical properties of lakes ( P <0.01). There was a strong correlation between pH and CDOM in the saline lakes, while DOC was significantly correlated with CDOM in the freshwater lakes ( P <0.05).

Currently, the systems for culturing buffalo spermatogonial stem cells (SSCs) in vitro are varied, and their effects are still inconclusive. In this study, we compared the effects of culture systems with undefined (foetal bovine serum) and defined (KnockOut Serum Replacement) materials on the in vitro culture of buffalo SSC-like cells. Significantly more DDX4- and UCHL1-positive cells (cultured for 2 days at passage 2) were observed in the defined materials culture system than in the undefined materials system ( p < 0.01), and these cells were maintained for a longer period than those in the culture system with undefined materials (10 days vs. 6 days). Furthermore, NANOS2 ( p < 0.05), DDX4 ( p < 0.01) and UCHL1 ( p < 0.05) were expressed at significantly higher levels in the culture system with defined materials than in that with undefined materials. Induction with retinoic acid was used to verify that the cultured cells maintained SSC characteristics, revealing an SCP3⁺ subset in the cells cultured in the defined materials system. The expression levels of Stra8 ( p < 0.05) and Rec8 ( p < 0.01) were significantly increased, and the expression levels of ZBTB16 ( p < 0.01) and DDX4 ( p < 0.05) were significantly decreased. These findings provided a clearer research platform for exploring the mechanism of buffalo SSCs in vitro ., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Korean Society of Veterinary Science.)

Background: Water buffalo ( Bubalus bubalis ) are divided into river buffalo and swamp buffalo subspecies and are essential livestock for agriculture and the local economy. Studies on buffalo reproduction have primarily focused on optimal fertility and embryonic mortality. There is currently limited knowledge on buffalo embryonic development, especially during the preimplantation period. Assembly of the river buffalo genome offers a reference for omics studies and facilitates transcriptomic analysis of preimplantation embryo development (PED)., Methods: We revealed transcriptomic profile of four stages (2-cell, 8-cell, Morula and Blastocyst) of PED via RNA-seq (Illumina HiSeq4000). Each stage comprised three biological replicates. The data were analyzed according to the basic RNA-seq analysis process. Ingenuity analysis of cell lineage control, especially transcription factor (TF) regulatory networks, was also performed., Results: A total of 21,519 expressed genes and 67,298 transcripts were predicted from approximately 81.94 Gb of raw data. Analysis of transcriptome-wide expression, gene coexpression networks, and differentially expressed genes (DEGs) allowed for the characterization of gene-specific expression levels and relationships for each stage. The expression patterns of TFs, such as POU5F1 , TEAD4 , CDX4 and GATAs , were elucidated across diverse time series; most TF expression levels were increased during the blastocyst stage, during which time cell differentiation is initiated. All of these TFs were involved in the composition of the regulatory networks that precisely specify cell fate. These findings offer a deeper understanding of PED at the transcriptional level in the river buffalo., Competing Interests: Ming-Zhou Bai, Chi Zhang, Junhui Chen and Zhihui Xiu are employed by BGI Genomics., (©2019 Pang et al.)

We aimed to identify QTL for serum electrolyte traits by performing a GWAS of calcium, chloride, sodium, potassium and magnesium ion concentrations in Chinese Holstein cattle. We detected five SNPs that had significant associations with calcium ion concentrations and identified GATA2 from Bos taurus chromosome (BTA)22 as having the highest significance. Among the genes with significant results, we speculate that TMEM123 might be related to calcium channel proteins according to the functions of the TMEM family., (© 2019 Stichting International Foundation for Animal Genetics.)