Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.

Identification and molecular mechanism of action of antibacterial peptides from Flavourzyme-hydrolyzed yak casein against Staphylococcus aureus.

Antibacterial peptides can be released from yak milk casein. To date, the amino acid sequences and mechanism of action of yak casein-derived antibacterial peptides remain unknown. The current study identified antibacterial peptides from yak casein and their molecular mechanism of action. Our results showed that yak α-casein, ß-casein, and κ-casein could be effectively hydrolyzed by Flavourzyme (Solarbio Science and Technology Co. Ltd.), and the 2-h hydrolysate showed the highest antibacterial rate of 43.07 ± 2.59% against Staphylococcus aureus. The 1,000 to 3,000 Da fraction accounted for 23.61% of the 2-h hydrolysate and had an antibacterial rate of 62.64 ± 4.40%. Three novel peptides with antibacterial activity were identified from this fraction, and the ß-casein-derived peptide APKHKEMPFPKYP showed the strongest antibacterial effect (half-maximal inhibitory concentration = 0.397 mg/mL). Molecular docking predicted that APKHKEMPFPKYP interacted with 2 important enzymes of Staph. aureus, dihydrofolate reductase and DNA gyrase, through hydrophobic, hydrogen bonding, salt bridge, and π-π stacking interactions. Our findings suggest that the yak casein-derived peptides may serve as a potential source of natural preservatives to inhibit Staph. aureus.

Metal Modulation: An Easy-to-Implement Tactic for Tuning Lanthanide Phototheranostics.

Phototheranostics constitute an emerging cancer treatment wherein the core diagnostic and therapeutic functions are integrated into a single photosensitizer (PS). Achieving the full potential of this modality requires being able to tune the photosensitizing properties of the PS in question. Structural modification of the organic framework represents a time-honored strategy for tuning the photophysical features of a given PS system. Here we report an easy-to-implement metal selection approach that allows for fine-tuning of excited-state energy dissipation and phototheranostics functions as exemplified by a set of lanthanide (Ln = Gd, Yb, Er) carbazole-containing porphyrinoid complexes. Femto- and nanosecond time-resolved spectroscopic studies, in conjunction with density functional theory calculations, revealed that the energy dissipation pathways for this set of PSs are highly dependent on the energy gap between the lowest triplet excited state of the ligand and the excited states of the coordinated Ln ions. The Yb complex displayed a balance of deactivation mechanisms that made it attractive as a potential combined photoacoustic imaging and photothermal/photodynamic therapy agent. It was encapsulated into mesoporous silica nanoparticles (MSN) to provide a biocompatible construct, YbL@MSN, which displays a high photothermal conversion efficiency (η = 45%) and a decent singlet oxygen quantum yield (ΦΔ = 31%). Mouse model studies revealed that YbL@MSN allows for both photoacoustic imaging and synergistic photothermal- and photodynamic-therapy-based tumor reduction in vivo. Our results lead us to suggest that metal selection represents a promising approach to fine-tuning the excited state properties and functional features of phototheranostics.

Capillary morphogenesis protein 2 is a novel prognostic biomarker and plays oncogenic roles in glioma.

Capillary morphogenesis protein 2 (CMG2) was originally identified through its participation in capillary morphogenesis, and subsequently identified as the second receptor for anthrax toxin (ANTXR2). Although tumor-associated functions of CMG2 have also been reported, the clinical significance and functional mechanism of CMG2 in glioma remain to be elucidated. We assessed the clinicopathological relevance of CMG2 in a cohort of 48 glioma patients as well as through public glioma databases, and explored the function of CMG2 using glioblastoma (GBM) models in vitro and in vivo. CMG2 overexpression was associated with increased tumor grade and poor patient survival. CMG2 promoted G2/M-phase transition during the cell cycle of GBM cells in vitro and contributed to tumor growth in vivo. We also observed that CMG2 is implicated in the activation of extracellular signal-regulated kinases (ERKs), epithelial-mesenchymal transition (EMT), migration, and invasion in GBM cells. Transcriptomic analysis of GBM cells with or without CMG2 overexpression indicated that a panel of oncogenic signaling pathways was altered with CMG2 upregulation, implying that CMG2 might orchestrate these signaling pathways to regulate the growth of GBM cells. Yes-associated protein 1 (YAP1) activity was enhanced by CMG2 overexpression but suppressed with CMG2 deficiency. Since YAP1 is critically implicated in GBM, the oncogenic roles of CMG2 in GBM cells might thus be mediated, at least partially, by YAP1. Altogether, CMG2 functioned as an oncogene in glioma cells and is a potential prognostic biomarker or therapeutic target for the clinical treatment of glioma. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Acupuncture for the treatment of obesity in adults: a systematic review and meta-analysis.

OBJECTIVE: Meta-analysis was used to assess the clinical efficacy of acupuncture treatment for simple obesity and to provide evidence-based medical data for treating obesity with acupuncture. METHODS: A comprehensive search of studies on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Chinese databases (Wan Fang,CNKI and VIP) from 1 January 1915 through 30 November 2015 (MEDLINE search updated through 31 December 2015) was performed. We included only randomised controlled trials (RCTs) that used acupuncture and sham acupuncture to treat simple obesity. The effect of acupuncture on simple obesity was measured using body mass index (BMI), body fat mass (BFM), waist circumference (WC), hip circumference (HC), and body weight (BW). The Jadad scale was used to assess methodological quality. The random effects model was used in the pooled analysis to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. The differences between treatment groups were reported as mean differences (MD). RESULTS: Eleven RCTs were selected after all relevant literature from the electronic databases had been screened. There were 338 and 305 participants in the acupuncture and sham acupuncture groups, respectively. Auricular and electro acupuncture were both able to reduce BMI in obese patients (MD 0.47 kg/m2, 95% CI 0.35 to 0.58, p<0.001; MD 0.50 kg/m2, 95% CI 0.38 to 0.62, p<0.001). BFM change after acupuncture treatment compared with sham treatment was statistically significant (MD 0.66 kg, 95% CI 0.51 to 0.80, p<0.001). There were also significant differences in WC and HC between the acupuncture and sham acupuncture groups (MDwc2.02 cm, 95% CI 0.21 to 3.83, p=0.03; MDHC2.74 cm, 95% CI 1.21 to 4.27, p=0.0004). BW was not statistically significantly different between the acupuncture and sham acupuncture groups (MD 0.60 kg, 95% CI -0.20 to 1.39, p=0.14). Begg's test and funnel plots showed that the potential publication bias of the included studies was very slight (p>0.05). CONCLUSION: Acupuncture for simple obesity appeared to be an effective treatment, but more studies on the safety of acupuncture used to treat simple obesity are required.

Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells.

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2minutes to 7hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.

[Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy].

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

UAV hyperspectral analysis of secondary salinization in arid oasis cotton fields: effects of FOD feature selection and SOA-RF.

Secondary salinization is a crucial constraint on agricultural progress in arid regions. The specific mulching irrigation technique not only exacerbates secondary salinization but also complicates field-scale soil salinity monitoring. UAV hyperspectral remote sensing offers a monitoring method that is high-precision, high-efficiency, and short-cycle. In this study, UAV hyperspectral images were used to derive one-dimensional, textural, and three-dimensional feature variables using Competitive adaptive reweighted sampling (CARS), Gray-Level Co-occurrence Matrix (GLCM), Boruta Feature Selection (Boruta), and Brightness-Color-Index (BCI) with Fractional-order differentiation (FOD) processing. Additionally, three modeling strategies were developed (Strategy 1 involves constructing the model solely with the 20 single-band variable inputs screened by the CARS algorithm. In Strategy 2, 25 texture features augment Strategy 1, resulting in 45 feature variables for model construction. Strategy 3, building upon Strategy 2, incorporates six triple-band indices, totaling 51 variables used in the model's construction) and integrated with the Seagull Optimization Algorithm for Random Forest (SOA-RF) models to predict soil electrical conductivity (EC) and delineate spatial distribution. The results demonstrated that fractional order differentiation highlights spectral features in noisy spectra, and different orders of differentiation reveal different hidden information. The correlation between soil EC and spectra varies with the order. 1.9th order differentiation is proved to be the best order for constructing one-dimensional indices; although the addition of texture features slightly improves the accuracy of the model, the integration of the three-waveband indices significantly improves the accuracy of the estimation, with an R2 of 0.9476. In contrast to the conventional RF model, the SOA-RF algorithm optimizes its parameters thereby significantly improving the accuracy and model stability. The optimal soil salinity prediction model proposed in this study can accurately, non-invasively and rapidly identify excessive salt accumulation in drip irrigation under membrane. It is of great significance to improve the growing conditions of cotton, increase the cotton yield, and promote the sustainable development of Xinjiang's agricultural economy, and also provides a reference for the prevention and control of regional soil salinization.

Laboratory tests and analysis of drug resistance in non-tuberculous mycobacteria.

Background: This study analyzed the laboratory diagnosis results and drug resistance of patients infected with non-tuberculous mycobacterium (NTM). Methods: We collected information on patients with positive indicators of NTM infection at the Henan Provincial Chest Hospital from 2020 to 2022. Acid-fast smear, mycobacterium culture, QB-SPOT assay, GeneXpert MTB/RIF assay, immunoglobulin E test, tuberculosis antibody test, and microplate method for drug sensitivity test were analyzed using strain identification as the gold standard. Results: The 242 cases of NTM infection were predominantly detected with slow-growing mycobacteria (a detection rate of 87.19%), among which Mycobacterium intracellulare (66.53%), Mycobacterium avium (15.70%), and Mycobacterium chelonei/abscessus complex (11.16%) ranked the top three in terms of the isolation rate. Males patients accounted for a higher proportion (58.26%) than females (41.74%), and the majority of them were over 60 years (50.83%). Among laboratory tests for patients with NTM infection, mycobacterium culture showed a highest detected rate (87.20%) among laboratory tests. The results of the drug sensitivity test demonstrated that the resistance rate of NTM was generally high. Moreover, the Mycobacterium avium complex with the highest isolation rate showed 100% resistant to doxycycline and minocycline, but exhibited relatively high sensitivity to moxifloxacin (a resistance rate of 7.89%) and rifabutin (a resistance rate of 13.16%). The Mycobacterium chelonei/abscessus complex was 100% resistant to doxycycline and relatively sensitive to cefoxitin (29.17%) and clarithromycin (37.50%). Conclusion: The NTM species isolated by the Henan Provincial Chest Hospital is dominated by Mycobacterium intracellulare and the highest positive rate is detected by mycobacterium culture among laboratory tests. NTM infection generally exhibits a high rate of drug resistance. Accordingly, the accurate diagnosis of NTM diseases requires enhanced drug sensitivity testing to provide patients with targeted combination drug treatment.

Managing Follicular Lymphoma in the Elderly Population.

Follicular lymphoma (FL) is one of the most commonly diagnosed types of indolent non-Hodgkin lymphoma (NHL). The median age of diagnosis for FL is 65 years old. Although the median life expectancy after diagnosis is approximately 10 years, the incurable disease has a high risk of transformation. This case report focuses on an 80-year-old patient diagnosed with low-grade follicular lymphoma which subsequently transformed leading to the patient's eventual demise as the patient took on the palliative intent. This case report aims to highlight the importance of clinical markers or prognostic factors to identify patients, specifically the elderly population who are at risk of transformation to aggressive forms when their FL remains at stage I-II phases. Currently, elderly patients with FL tend to be quickly dismissed with curative intent with chemotherapy, given their age and comorbidities, despite forming the majority of the population with follicular lymphoma. Age more than 60 years old has been shown to be one of the most powerful yet poor prognostic features in follicular lymphoma international prognostic index (FLIPI)-the main scoring system used for FL. Hence, further studies are required to look into the tailoring treatment for elderly patients with follicular lymphoma after risk stratifying them with appropriate clinical and prognostic markers.

Degradation Characteristics of Cellulose Acetate in Different Aqueous Conditions.

Cellulose acetate (CA) is widely used in cigarette filters and packaging films, but due to its acetylation, it is difficult to degrade in the natural environment, and the problem of pollution has become a serious challenge. Understanding the degradation behavior and performance of CA in different environments is the basis and prerequisite for achieving its comprehensive utilization and developing efficient degradation methods. In this study, we investigated the degradation performance of CA in different aqueous environments to evaluate the effects of pH, salinity and microorganisms on CA degradation. The CA tows and films were immersed in HCl, NaOH solution, river water, seawater or homemade seawater for 16 weeks and the degradation mechanism was investigated by the changes in weight loss rate, degree of substitution, hydrophilicity, molecular structure and surface morphology. The results showed that the degradation of CA tow and film were the fastest in NaOH solution; the weight loss rates after 16 weeks were 40.29% and 39.63%, respectively, followed by HCl solution, and the degradation performance of CA tow was better than that of film. After 16 weeks of degradation in river water, seawater and homemade seawater, all the weight loss rates were less than 3%. In summary, this study illustrated that the environmental acidity, basicity and high concentration of inorganic salts had a critical promotion effect on the non-enzymatic hydrolysis of CA, whereas the number and type of microorganisms were the key factors affecting the biodegradation of CA.

The influence of membrane molecular weight cutoff on a novel bioartificial liver.

Given the xenogeneic immune reaction relevant to the molecular weight cutoff of the membrane of a bioartificial liver (BAL) system, we investigated the influence of membrane molecular weight cutoff in our BAL system in this study. Acute liver failure in beagles was induced by d-galactosamine administration. Eight beagles were divided into two groups by the membrane molecular weight cutoff of the plasma component separator. Group 1 beagles were treated with BAL containing 200 kDa retention rating membrane. Group 2 beagles were treated with BAL containing 1200 kDa retention rating membrane. Each group underwent two 6-h BAL treatments that were performed on day 1 and day 21. The hemodynamic and hematologic response, humoral immune responses, and cytotoxic immune response to BAL therapy were studied before and after treatments. All beagles remained hemodynamically and hematologically stable during BAL treatments. BAL treatment was associated with a significant decline in levels of complement; however, a longer time of level maintenance was observed in Group 2. Group 2 beagles experienced a significant increase in levels of IgG and IgM after two BAL treatments. Significant levels of canine proteins were detected in BAL medium from Group 2; only trace levels of canine proteins were detected in BAL medium from Group 1. The posttreatment viability of co-culture cells in Group 2 was lower compared with Group 1, and the viability of co-culture cells after treatments was associated with deposition of canine proteins on the cells. Xenogeneic immune response was influenced by membrane molecular weight cutoff in the BAL.

Validity and Reliability of Semiquantitative Food Frequency Questionnaires for Assessing Nutrient Intake among Preschool Children in Northwest China.

BACKGROUND: Considering the lack of valid and reliable food frequency questionnaires (FFQs) for nutritional epidemiological studies in China, it is necessary to develop an effective one for assessing nutrient intake among preschool children. The aim of this study was to evaluate the validity and reliability of newly developed FFQs for assessing food and nutrient intakes among preschool children in Northwest China. METHODS: Semiquantitative 67-item FFQs were developed and validated. In total, 326 children (aged 2-6 years) were recruited from three different cities in Northwest China. All subjects were asked to complete the FFQs twice with a six-month interval period for test-retest reliability. Apart from the FFQs, a 3-day food record (3-DFR) was also carried out to evaluate the validity of the FFQs. RESULTS: There was no significant difference in the nutrient intakes of preschool children between the two FFQs (P > 0.05), and these two FFQs demonstrated a positive correlation (P < 0.05). Spearman's coefficient correlation values ranged from 0.222 ("Selenium") to 0.832 ("Energy"). The intraclass correlation coefficient values ranged from 0.282 ("Selenium") to 0.882 ("Energy"). With regards to the validity of FFQs, nutrient intakes from FFQs were greater than 3DR dietary recalls (P < 0.05). After adjusting for total energy and intraindividual variation, all nutrient intakes showed a positive correlation (P < 0.05), and these correlations became stronger. According to the quartiles of nutrient intakes, the exact agreement between the FFQs and 3DR dietary recalls ranged between 40% ("Selenium") and 70% ("Energy"), and grossly misclassified was low (12.5%). CONCLUSIONS: The findings of this study indicate that the designed FFQs exhibit good test-retest reliability and moderate relative validity. Hence, the FFQs can serve as an important tool for the large-scale assessment of food and nutrient intakes among preschool children (in the mentioned areas of China).

Association of lncRNA H19 polymorphisms with cancer susceptibility: An updated meta-analysis based on 53 studies.

The association between polymorphisms in lncRNA H19 and cancer susceptibility remains to be inconsistent. This study aimed to provide a more precise estimation of the relationship between lncRNA H19 polymorphisms and the risk of cancer based on all available published studies. 53 studies encompassing 32,376 cases and 43,659 controls were included in our meta-analysis by searching the Pubmed, Embase, Web of Science, WanFang, and China National Knowledge Infrastructure databases. Pooled ORs and their 95% CIs were used to estimate the strength between the SNPs in H19 (rs217727, rs2839698, rs2107425, rs3024270, rs2735971, rs3741216, and rs3741219) and cancer susceptibility. The results showed that H19 rs2839698 polymorphism was associated with increased cancer risk in all participants under three genetic models. However, no significant association was identified between the other six SNPs as well as an overall cancer risk. Stratification by ethnicity showed that rs2839698 mutation indicated to be an important hazardous factor for the Asian population. While rs2107425 mutation had a protective effect on the Caucasian population. Stratification by cancer type identified that rs217727 mutation was linked to increased susceptibility to oral squamous cell carcinoma, lung cancer, and hepatocellular carcinoma; whereas rs2839698 mutation was associated with an elevated risk of hematological tumor and digestive system tumor (p < 0.05). Besides, the rs2735971 mutation was connected with the digestive system tumor. In summary, the rs217727, rs2839698, rs2107425 and rs2735971 polymorphisms in H19 have associations with cancer susceptibility.

Tenebrio molitor Proteins-Derived DPP-4 Inhibitory Peptides: Preparation, Identification, and Molecular Binding Mechanism.

Inhibition of dipeptidyl peptidase-4 (DPP-4) is an effective way to control blood glucose in diabetic patients. Tenebrio (T.) molitor is an edible insect containing abundant protein. T. molitor protein-derived peptides can suppress the DPP-4 activity. However, the amino acid sequence and binding mechanism of these DPP-4 inhibitory peptides remain unclear. This study used the flavourzyme for T. molitor protein hydrolysis, identified the released peptides with DPP-4 inhibitory effect, and investigated the binding interactions of these peptides with DPP-4. The results showed that flavourzyme efficiently hydrolyzed the T. molitor protein, as demonstrated by the high degree of hydrolysis, disappearance of protein bands in SDS-PAGE, and changes to protein structure. The 4-h flavourzyme hydrolysates showed a good inhibitory effect on DPP-4 (IC50 value of 1.64 mg/mL). The fragment of 1000-3000 Da accounted for 10.39% of the total peptides, but showed the strongest inhibitory effect on DPP-4. The peptides LPDQWDWR and APPDGGFWEWGD were identified from this fraction, and their IC50 values against DPP-4 were 0.15 and 1.03 mg/mL, respectively. Molecular docking showed that these two peptides interacted with the DPP-4 active site via hydrogen bonding, hydrophobic interactions, salt bridge formation, π-cation interactions, and π-π stacking. Our findings indicated that T. molitor protein-derived peptides could be used as natural DPP-4 inhibitors.

A five-year review of prevalence and treatment outcomes of pre-extensively drug-resistant plus additional drug-resistant tuberculosis in the Henan Provincial Tuberculosis Clinical Medicine Research Centre.

OBJECTIVES: This study investigated the prevalence and significant clinical outcomes of pre-extensively drug-resistant plus additional drug-resistant tuberculosis (pre-XDR-plus) in Henan Provincial Chest Hospital between 2017 and 2021. METHODS: We analysed and summarized the drug sensitivity test (DST) results of clinical Mycobacterium tuberculosis (MTB) strains in TB patients seeking care in the Tuberculosis Clinical Medical Research Centre of Henan Province between 2017 and 2021. Medical records of pre-extensively drug-resistant plus additional drug-resistant TB patients were statistically analysed, including demographic characteristics, regimens, and outcomes. RESULTS: Of the 3689 Mycobacterium tuberculosis strains, 639 (17.32%), 353 (9.56%), and 109 (2.95%), multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (pre-XDR), and pre-XDR-plus, respectively. The proportion of MDR decreased from 19.1% in 2017 to 17.5% in 2021 (χ2 = 0.686, P = 0.407), the proportion of pre-XDR from 11.4% in 2017 to 9.0% in 2021 (χ2 = 2.39, P = 0.122), and pre-XDR-plus from 4.7% in 2017 to 1.8% in 2020, with the declining trend was significant (χ2 = 9.348, P = 0.002). The most commonly used anti-TB drugs were pyrazinamide (PZA, 37/46, 80.43%) and cycloserine (CS, 32/46, 69.57%), followed by linezolid (LZD, 25/46, 54.35%), protionamide (TH, 25/46, 54.35%), and para-aminosalicylic acid (PAS, 23/46, 50.00%). Patients receiving the LZD regimen were 5 times more likely to have a favourable outcome than those not receiving LZD (OR = 6.421, 95% CI 2.101-19.625, P = 0.001). Patients receiving a regimen containing CS were 4 times more likely to have a favourable outcome compared to those not taking CS (OR = 5.444, 95% CI 1.650-17.926, P = 0.005). CONCLUSIONS: Our data suggest that the population of pre-XDR-plus had significantly decreased over the past five years in the Henan Provincial Chest Hospital. The COVID-19 and flood disaster affect TB patients' selection of medical services. In addition, the pre-XDR-plus patients whose regimens contain LZD or CS were more likely to have favourable outcomes.

Fluorescence-based monitoring of the pressure-induced aggregation microenvironment evolution for an AIEgen under multiple excitation channels.

The development of organic solid-state luminescent materials, especially those sensitive to aggregation microenvironment, is critical for their applications in devices such as pressure-sensitive elements, sensors, and photoelectric devices. However, it still faces certain challenges and a deep understanding of the corresponding internal mechanisms is required. Here, we put forward an unconventional strategy to explore the pressure-induced evolution of the aggregation microenvironment, involving changes in molecular conformation, stacking mode, and intermolecular interaction, by monitoring the emission under multiple excitation channels based on a luminogen with aggregation-induced emission characteristics of di(p-methoxylphenyl)dibenzofulvene. Under three excitation wavelengths, the distinct emission behaviors have been interestingly observed to reveal the pressure-induced structural evolution, well consistent with the results from ultraviolet-visible absorption, high-pressure angle-dispersive X-ray diffraction, and infrared studies, which have rarely been reported before. This finding provides important insights into the design of organic solid luminescent materials and greatly promotes the development of stimulus-responsive luminescent materials.

The value of Xpert MTB/RIF assay of urine samples in the early diagnosis of smear-negative urinary tuberculosis.

BACKGROUND: According to reports, between 30 and 40 percent of extrapulmonary tuberculosis (EPTB) cases are caused by urinary tract tuberculosis (UTB). It is critical to identify UTB quickly since it frequently precedes delayed medical attention, which can have detrimental effects. This study examined the use of Xpert MTB/RIF, a PCR test that can detect MTB as well as resistance to an important drug, rifampicin (RIF), in UTB particularly, for the early identification of UTB. METHODS: 180 participants with clinically presumptive UTB whose urine samples were chosen for urine sediment smear, culture, Xpert MTB/RIF, and TB-DNA testing at Henan Chest Hospital between January 2019 and July 2022. Evaluation of test performance using Composite Reference Standards (CRSs). We studied and compared the positivity rate for various tests using the t-test. The effectiveness of smear, culture, Xpert MTB/RIF, and TB-DNA was assessed using McNemar test. RESULTS: In this subject, a total of 108 participants were diagnosed with UTB, and the positivity rate was 67.1%. Compared with CRS, the positivity rate of Xpert MTB/RIF, smear, culture, and TB-DNA was 29.69% (19/64, P < 0.001), 7.56% (9/119, P < 0.1), 12.12% (4/33, P > 0.05), and 18.75% (6/32, P < 0.1), respectively. The sensitivity of Xpert MTB/RIF assay was significantly better than that of smear and culture tests (78.9% vs. 77.8%, P < 0.05; 78.9% vs. 75%, P < 0.05). Under CRS, the positivity rate for Xpert, culture, and TB-DNA was 31.6% (6/19, P < 0.1), 6.2% (1/16, P > 0.05), and 26.7% (4/15, P > 0.05) for TB-DNA, respectively, compared to smear negative. Xpert MTB/RIF assay specificity was significant for culture and TB-DNA (53.6% vs. 25%, P < 0.01; 53.6% vs. 38.9%, P < 0.05), and Xpert MTB/RIF assay FPV was significant for culture and TB-DNA (53.6% vs. 0%, P < 0.001; 53.6% vs. 0%, P < 0.001). CONCLUSION: Xpert MTB/RIF outperforms smear, cultures, and TB-DNA in detecting UTB, plus Xpert MTB/RIF is better suited for early diagnosis in smear-negative UTB.

Effects of membrane molecular weight cutoff on performance of a novel bioartificial liver.

Immunoisolation using semipermeable membranes has been incorporated into bioartificial liver (BAL) devices to separate cellular components of the recipient's immune system from the cells within the BAL device. This study was designed to explore the influence of membrane molecular weight cutoff on performance of the multilayer radial-flow BAL using porcine hepatocytes cocultured with mesenchymal stem cells. In this study, healthy beagles underwent 6-h treatment with a BAL containing membrane with 200 kDa retention rating or 1200 kDa retention rating. Functional markers of BAL performance were monitored before and after treatment, as well as cytotoxic immune response to BAL therapy. The results showed that hepatocyte performance levels such as albumin secretion, urea synthesis, and viability were all significantly higher in 200 kDa retention rating group compared with the 1200 kDa retention rating group after treatment (P < 0.05). Significant levels of canine proteins were detected in BAL medium from the 1200 kDa retention rating group. Fluorescence microscopy further verified that heavy deposition of canine IgG, IgM, and complement (C3) on coculture cells was obtained after BAL treatment in the 1200 kDa retention rating group. However, only trace deposits of canine immunoproteins were observed on coculture cells obtained from BAL in the 200 kDa retention rating group. Small membrane molecular weight cutoff of the BAL could reduce the transfer of xenoreactive antibodies into the BAL medium and improve the performance of the BAL.