Establishment of a humanized ST6GAL1 mouse model for influenza research.

BACKGROUND: This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1. METHODS: Humanized fragments, consisting of the endothelial cell-specific K18 promoter, human ST6GAL1-encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed. RESULTS: Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range. CONCLUSION: A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Probing Intra-Gap States Mediated Charge Dynamics of Rh-Doped Rutile TiO2 Photocatalyst by Light-Modulated Photocurrent Spectroscopies.

The intra-gap states that are introduced into a semiconducting photocatalyst via dopants and other defects have significant implications on the transport dynamics of photoexcited electrons and holes during an aqueous light-driven reaction. In this work, mechanistic understanding of Rh-doped rutile, a promising photocatalyst for hydrogen production from water, is gained by systematic assessment combining intensity-modulated photocurrent spectroscopy with sub-gap excitations and alternating-current photocurrent spectroscopy. These operando techniques not only help in discovering a new electronic transport path in Rh-rutile via surface Rh4+ species and elucidating complex interaction between electrolyte molecules and semiconductors, but also underscore the potential of utilizing multiple sub-gap excitations synergistically. This combination offers a powerful tool for acquiring insight into photo-physical and photo-chemical behaviors of photo(electro)catalysts with intra-gap states.

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis.

ABSTRACT: Male germ cells employ specific metabolic pathways throughout their developmental stages. In a previous study, we discovered heightened expression of pyruvate kinase M (PKM), a pivotal glycolytic enzyme, in spermatogonia and spermatids. To gain deeper insights into PKM's roles in spermatogenesis, sperm function, and male fertility, we engineered a conditional-knockout mouse model (Pkm-vKO mice) to selectively disrupt the Pkm gene within germ cells. Despite maintaining regular testicular histology and sperm morphology, the male Pkm-vKO mice were infertility, characterized by significant impairments in sperm motility and adenosine triphosphate (ATP) generation. In addition, Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation, as well as compromised performance in in vitro fertilization experiments. To conclude, PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells; however, it emerges as a critical factor influencing sperm motility and overall male fertility.

Treatment outcomes of multidrug-resistant tuberculosis patients receiving ambulatory treatment in Shenzhen, China: a retrospective cohort study.

Background: WHO recommended multidrug-resistant tuberculosis (MDR-TB) should be treated mainly under ambulatory model, but outcome of ambulatory treatment of MDR-TB in China was little known. Methods: The clinical data of 261 MDR-TB patients treated as outpatients in Shenzhen, China during 2010-2015 were collected and analyzed retrospectively. Results: Of 261 MDR-TB patients receiving ambulatory treatment, 71.1% (186/261) achieved treatment success (cured or completed treatment), 0.4% (1/261) died during treatment, 11.5% (30/261) had treatment failure or relapse, 8.0% (21/261) were lost to follow-up, and 8.8% (23/261) were transferred out. The culture conversion rate at 6 months was 85.0%. Although 91.6% (239/261) of patients experienced at least one adverse event (AE), only 2% of AEs caused permanent discontinuation of one or more drugs. Multivariate analysis showed that previous TB treatment, regimens containing capreomycin and resistance to FQs were associated with poor outcomes, while experiencing three or more AEs was associated with good outcomes. Conclusion: Good treatment success rates and early culture conversions were achieved with entirely ambulatory treatment of MDR-TB patients in Shenzhen, supporting WHO recommendations. Advantageous aspects of the local TB control program, including accessible and affordable second-line drugs, patient support, active monitoring and proper management of AEs and well-implemented DOT likely contributed to treatment success rates.

Recent molecular design strategies for efficient photodynamic therapy and its synergistic therapy based on AIE photosensitizers.

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.

Correlation Analysis between the Emotion and Aesthetics for Chinese Classical Garden Design Based on Deep Transfer Learning.

Garden design with healthy psychological characteristics is a design method that mines positive psychological expressions and converts them into garden design elements. Chinese classical gardens are cultural heritage of China. Studying the beauty of space in classical gardens is of great significance to inheriting traditional culture, traditional art, and traditional aesthetics. At present, the research hotspots of garden design with healthy psychological characteristics mainly focus on the construction of relevant research theories and methods with the help of various intelligent tools. In this study, we propose a deep learning-based end-to-end model to recognize the positive psychological design of a Chinese classical garden. The model is designed based on Inception V3 that is proposed by Google. The innovation lies in that transfer learning which is integrated into Inception V3 to improve the generalization ability. Also, it is not necessary to encode the characteristics of the garden design style due to the end-to-end structure used in our proposed model. We design a positive psychological characteristics classification task to recognize high aesthetic feeling and low aesthetic feeling of rockery design. Experimental results indicate that our proposed model wins the best performance compared with other comparison models.

Predictors and Trends of MDR/RR-TB in Shenzhen China: A Retrospective 2012-2020 Period Analysis.

PURPOSE: We analyzed the trends and predictors of multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis (TB) in culture-positive cases in Shenzhen during 2012-2020, after the implementation of improved strategies (scale-up molecular drug susceptibility testing [mDST], expansion of DST eligibility, and generous reimbursement of MDR-TB outpatient care costs). MATERIALS AND METHODS: We retrospectively extracted and analyzed data from the TB Information System on drug-resistant pulmonary tuberculosis diagnosed in Shenzhen during the 2012-2020 period. We analyzed trends in RR- and MDR-TB rates in new cases during 2012-2018 and 2018-2020 periods, and among previously-treated cases during 2012-2017 and 2017-2020 periods, using Cochran-Armitage tests. We generated multivariate logistic regression models to analyze demographic predictors of MDR/RR-TB rates. RESULTS: We found 21,367 positive mycobacterial cultures in Shenzhen during the 2012-2020 period, and 19,951 (93.4%) were identified as Mycobacterium tuberculosis and had DST results (92.0% of those were mDST-based). Of these patients with DST results, 1630 (8.2%) were RR-TB, and 1142 (5.7%) were MDR-TB. Of the RR-TB, 70% were MDR-TB. The MDR/RR-TB rate in new TB cases increased significantly during the 2012-2018 period (P trend < 0.05), but it decreased in the 2018-2020 period (P trend > 0.05, with a significant trend for MDR-TB). Among previously treated cases, the temporal MDR/RR-TB rate trends did not differ significantly (P trend > 0.05). Our multivariate analysis showed that age younger than 30 years, housework service/unemployment, local residency, and previous TB treatment were all predictors of MDR/RR-TB. The percentage of patients with MDR-TB on treatment increased from 49.4% in 2012 to 70.5% in 2020. The treatment success rate of patients with MDR-TB during the 2012-2018 period was 71%. CONCLUSION: During the study period in Shenzhen, the cases of MDR/RR-TB were detected, and the treatment enrollment increased and the MDR-TB rates decreased gradually after 2017. Decreasing trends may reflect the efficacy of improved strategies; however, their long-term impact on the MDR-TB burden remains to be investigated. The predictors of MDR-TB identified in our study should be considered when developing targeted MDR-TB control strategies.

SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role.

In December 2019, a pneumonia outbreak of unknown etiology was reported which caused panic in Wuhan city of central China, which was later identified as Coronavirus disease (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CDC) and WHO. To date, the SARS-CoV-2 spread has already become a global pandemic with a considerable death toll. The associated symptoms of the COVID-19 infection varied with increased inflammation as an everyday pathological basis. Among various other symptoms such as fever, cough, lethargy, gastrointestinal (GI) symptoms included diarrhea and IBD with colitis, have been reported. Currently, there is no sole cure for COVID-19, and researchers are actively engaged to search out appropriate treatment and develop a vaccine for its prevention. Antiviral for controlling viral load and corticosteroid therapy for reducing inflammation seems to be inadequate to control the fatality rate. Based on the available related literature, which documented GI symptoms with diarrhea, inflammatory bowel diseases (IBD) with colitis, and increased deaths in the intensive care unit (ICU), conclude that dysbiosis occurs during SARS-COV-2 infection as the gut-lung axis cannot be ignored. As probiotics play a therapeutic role for GI, IBD, colitis, and even in viral infection. So, we assume that the inclusion of studies to investigate gut microbiome and subsequent therapies such as probiotics might help decrease the inflammatory response of viral pathogenesis and respiratory symptoms by strengthening the host immune system, amelioration of gut microbiome, and improvement of gut barrier function.

[Neutrophil-lymphocyte ratio at 14th week predicts loss of response to 52-week infliximab therapy in patients with Crohn's disease].

OBJECTIVE: Loss of response (LOR) has become an important clinical problem in patients with Crohn's disease receiving infliximab (IFX) treatment. Neutrophil-lymphocyte ratio (NLR) has been shown to correlate with the activity of inflammatory bowel disease (IBD), and NLR at the 14th week of IFX therapy potentially allows the prediction of sustained response to IFX in Crohn's patients. The aim of this study was to explore whether NLR at the 14th week of IFX therapy could predict the occurrence of LOR to IFX in Crohn's patients. METHODS: Between January, 2012 and December, 2016, 54 patients with Crohn's disease underwent a 52-week treatment with IFX and successfully achieved response to the induction treatment in Zhongnan Hospital. We retrospectively examined their medical records and assessed the association between NLR at 14 weeks and LOR during IFX therapy. RESULTS: Of the 54 patients, 15 (27.8%) showed LOR to IFX during the follow-up. We noted a significant increase in NLR at 14 weeks in the patients with LOR as compared with the patients with sustained response to IFX[3.51 (2.9-6.25) vs 1.77 (1.23-2.56), P=0.00]. Receiver-operating characteristic analysis showed that at the cut-off value of 2.75, NLR at 14 weeks was predictive of LOR within 52 weeks of IFX therapy with a sensitivity of 93.33% and a specificity of 84.62%, and the area under curve (AUC) of NLR was 0.903 (0.731-0.959). Univariate analysis revealed a significant correlation between relapse-free survival and the NLR at 14 weeks (P=0.00). Multivariate analysis identified NLR at 14 weeks as an independent prognostic factor for LOR with a hazard ratio of 1.851 (95% CI:1.096-3.026, P=0.021). CONCLUSIONS: NLR at the 14th week during IFX therapy is a useful predictor for LOR in patients with Crohn's disease.

Propensity score analysis of outcomes between the transabdominal preperitoneal and open Lichtenstein repair techniques for inguinal hernia repair: a single-center experience.

BACKGROUND: The mechanism of persistent chronic pain after TAPP and OLR remains controversial. Therefore, more prospective and well-designed studies are needed to determine the predictive risk factors that will lead to better pain prevention and possibly elimination. The aim of the present study was to investigate the risk factors of chronic pain after TAPP repair and OLR in a single institution. METHODS: A single-center, retrospective study of propensity score-matched patients who underwent TAPP or OLR surgery between 2008 and 2018 was conducted. To overcome selection bias, we performed 1:1 matching using 6 covariates to generate the propensity score. RESULTS: A total of 400 patients treated with TAPP and 424 patients treated with OLR were balanced to 400 pairs of matched patients. The patients' age (P < 0.001), BMI (P < 0.001), foreign body sensation within 3 months after surgery (P < 0.001), and persistent sensation loss (P = 0.002) were different between the two groups. The OLR group had a shorter operative time than did the TAPP group (P < 0.001). The univariate analysis of factors predicting a difference in VAS between the preoperative assessment and the assessment 3 months after surgery showed that the type of surgery (P = 0.004), hernia grade (P = 0.001), type of mesh (P < 0.001), presence of scrotal invasion (P = 0.024), and foreign body sensation within 3 months (P = 0.047) were risk factors. The multivariate analysis revealed that only hernia grade III (CI - 8.524, - 2.783; P < 0.001), OLR operation type (CI 1.069, 4.987; P = 0.002), and the use of polypropylene mesh (CI - 5.400, - 1.489; P = 0.001) were independently associated with chronic pain. CONCLUSION: These results suggest that compared to OLR, TAPP leads to less postoperative pain and a better long-term quality of life.

Efficient Biosynthesis of Natural Yellow Pigments by Monascus purpureus in a Novel Integrated Fermentation System.

Because of the increasing demand for healthy and safe food, Monascus spp. have gained much attention as a sustainable source of natural food colorant. In this study, a novel integrated fermentation system consisting of surfactant and in situ extractant was established for efficiently producing yellow pigments by M. purpureus sjs-6. The maximum production of Monascus yellow pigment (669.2 U/mL) was obtained when 40% soybean oil (as extractant) was supplied at the beginning and 5 g/L Span-80 (as surfactant) was supplied at the 72nd h, which resulted in production 27.8-times of that of the control. Critical factors such as alleviating the product inhibition, increasing the membrane permeability, changing the hyphal morphology, and influencing the cell activity have been suggested as the underlying mechanisms. This system is of great significance for the bioprocess, which suffers product inhibition, and it can serve as a promising step for enhancing the yield of hydrophobic metabolites.

[Identification of a myeloid differentiation factor 88 (MyD88) in Oncomelania hupensis against Schistosoma japonicum infection].

OBJECTIVE: To identify a myeloid differentiation factor 88 (MyD88) in Oncomelania hupensis, and characterize the role of MyD88 against Schistosoma japonicum infection. METHODS: The complete cDNA of MyD88 in O. hupensis was obtained by using rapid amplification of cDNA ends (RACE), and homologues sequences and conserved domains were aligned and the structure of MyD88 was predicted either. A phylogenetic tree of MyD88 was further constructed with other species. In addition, the mRNA expression level of O. hupensis MyD88 before and after S. japonicum infection was investigated by real-time quantitative PCR (RT-qPCR). RESULTS: The cDNA of O. hupensis MyD88 consisted of 1 406 bp open reading frame (ORF), encoding 468 amino acid residues, which contained death domain and Toll/interlrukin-1 receptor (TIR) domain, the typical features of MyD88 family proteins. The predicted amino acid sequence of O. hupensis MyD88 shared 38%-52% identity with other mollusc. O. hupensis MyD88 was phylogenetically closeted to Biomphalaria glabrata MyD88. The O. hupensis MyD88 existed in all selected tissues and expressed highly in hemocyte, up-regulated after S. japonicum infection in all selected tissues except cephalopodium, especially higher in whole snail and hemocyte. CONCLUSIONS: MyD88-dependent signaling pathway is present in O. hupensis and plays an important role in innate immune response against S. japonicum infection.

A multiresidue method for 20 pesticides in Radix paeoniae Alba of Chinese herb by gas chromatography with electron-capture detection.

A rapid multiresidue method was developed for the determination of 20 pesticides in Radix paeoniae Alba of Chinese herb by ultrasonic wave extraction, silica gel column chromatography and gas chromatography (GC) with electron-capture detection (ECD) in this study, Mean recoveries of the method ranged from 74.45 to 115.14%. The validation of the proposed approach was verified on Isatis indigotica Fort, Pltycodon grandiflorum, Cotex mouta and Poria cocos of Chinese herbs; good recoveries were also obtained in the range of 72.51-113.47%, respectively.