Dendritic cell targeting peptide plus Salmonella FliCd flagellin fused outer membrane protein H (OmpH) demonstrated increased efficacy against infections caused by different Pasteurella multocida serogroups in mouse models.

As the major outer membrane protein (OMP) presents in the Pasteurella multocida envelope, OmpH was frequently expressed for laboratory assessments of its immunogenicity against P. multocida infections, but the results are not good. In this study, we modified OmpH with dendritic cell targeting peptide (Depeps) and/or Salmonella FliCd flagellin, and expressed three types of recombinant proteins with the MBP tag (rDepeps-FliC-OmpH-MBP, rDepeps-OmpH-MBP, rFliC-OmpH-MBP). Assessments in mouse models revealed that vaccination with rDepeps-FliC-OmpH-MBP, rDepeps-OmpH-MBP, or rFliC-OmpH-MBP induced significant higher level of antibodies as well as IFN-γ and IL-4 in murine sera than vaccination with rOmpH-MBP (P < 0.5). Vaccination with the three modified proteins also provided increased protection (rDepeps-FliC-OmpH-MBP, 70 %; rDepeps-OmpH-MBP, 50 %; rFliC-OmpH-MBP, 60 %) against P. multocida serotype D compared to vaccination with rOmpH-MBP (30 %). In mice vaccinated with different types of modified OmpHs, a significantly decreased bacterial strains were recovered from bloods, lungs, and spleens compared to rOmpH-MBP-vaccinated mice (P < 0.5). Notably, our assessments also demonstrated that vaccination with rDepeps-FliC-OmpH-MBP provided good protection against infections caused by a heterogeneous group of P. multocida serotypes (A, B, D). Our above findings indicate that modification with DCpep and Salmonella flagellin could be used as a promising strategy to improve vaccine effectiveness.

Trends in the Prevalence of Common Retinal and Optic Nerve Diseases in China: An Artificial Intelligence Based National Screening.

Purpose: Retinal and optic nerve diseases have become the primary cause of irreversible vision loss and blindness. However, there is still a lack of thorough evaluation regarding their prevalence in China. Methods: This artificial intelligence-based national screening study applied a previously developed deep learning algorithm, named the Retinal Artificial Intelligence Diagnosis System (RAIDS). De-identified personal medical records from January 2019 to December 2021 were extracted from 65 examination centers in 19 provinces of China. Crude prevalence and age-sex-adjusted prevalence were calculated by mapping to the standard population in the seventh national census. Results: In 2021, adjusted referral possible glaucoma (63.29, 95% confidence interval [CI] = 57.12-68.90 cases per 1000), epiretinal macular membrane (21.84, 95% CI = 15.64-29.22), age-related macular degeneration (13.93, 95% CI = 11.09-17.17), and diabetic retinopathy (11.33, 95% CI = 8.89-13.77) ranked the highest among 10 diseases. Female participants had significantly higher adjusted prevalence of pathologic myopia, yet a lower adjusted prevalence of diabetic retinopathy, referral possible glaucoma, and hypertensive retinopathy than male participants. From 2019 to 2021, the adjusted prevalence of retinal vein occlusion (0.99, 95% CI = 0.73-1.26 to 1.88, 95% CI = 1.42-2.44), macular hole (0.59, 95% CI = 0.41-0.82 to 1.12, 95% CI = 0.76-1.51), and hypertensive retinopathy (0.53, 95% CI = 0.40-0.67 to 0.77, 95% CI = 0.60-0.95) significantly increased. The prevalence of diabetic retinopathy in participants under 50 years old significant increased. Conclusions: Retinal and optic nerve diseases are an important public health concern in China. Further well-conceived epidemiological studies are required to validate the observed increased prevalence of diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion, and macular hole nationwide. Translational Relevance: This artificial intelligence system can be a potential tool to monitor the prevalence of major retinal and optic nerve diseases over a wide geographic area.

Discovery of the tigecycline resistance gene cluster tmexCD3-toprJ1 in Pasteurella multocida strains isolated from pigs in China.

Pasteurella multocida is a leading cause of respiratory disorders in pigs. However, the genotypes and antimicrobial resistance characteristics of P. multocida from pigs in China have not been reported frequently. In this study, we investigated 381 porcine strains of P. multocida collected in China between 2013 and 2022. These strains were assigned to capsular genotypes A (69.55%, n = 265), D (27.82%, n =106), and F (2.62%, n = 10); or lipopolysaccharide genotypes L1 (1.31%, n = 5), L3 (24.41%, n = 93), and L6 (74.28%, n = 283). Overall, P. multocida genotype A:L6 (46.46%) was the most-commonly identified type, followed by D:L6 (27.82%), A:L3 (21.78%), F:L3 (2.62%), and A:L1 (1.31%). Antimicrobial susceptibility testing showed that a relatively high proportion of strains were resistant to tetracycline (66.67%, n = 254), and florfenicol (35.17%, n = 134), while a small proportion of strains showed resistance phenotypes to enrofloxacin (10.76%, n = 41), ampicillin (8.40%, n = 32), tilmicosin (7.09%, n = 27), and ceftiofur (2.89%, n = 11). Notably, Illumina short-read and Nanopore long-read sequencing identified a chromosome-borne tigecycline-resistance gene cluster tmexCD3-toprJ1 in P. multocida. The structure of this cluster was highly similar to the respective structures found in several members of Proteus or Pseudomonas. It is assumed that the current study identified the tmexCD3-toprJ1 cluster for the first time in P. multocida.

Superoxide dismutase alterations in COVID-19: implications for disease severity and mortality prediction in the context of omicron variant infection.

Background: In the few reports to date, the changes in superoxide dismutase (SOD), a key factor in cellular protection against superoxide, in COVID-19 have been very inconsistent and contradictory. There is also a lack of data on COVID-19 induced by Omicron variant. Further investigation is warranted to figure out SOD alterations in COVID-19, particularly within the context of ongoing Omicron variant infection, which may provide clues to its role within COVID-19 pathogenesis and open up new avenues for COVID-19 treatment. Methods: SOD activity in 109 COVID-19 patients (including 46 severe cases and 63 mild to moderate cases) and 30 matched healthy controls were quantified. Demographic data, blood cell counts, biochemical indicators, coagulation indicators, and inflammatory markers were also recorded. Results: SOD, an important key node, experienced a significant decrease in COVID-19, with the severe patients exhibiting lower activity compared to the mild to moderate patients and control healthy. Notably, severe patients who deceased had the lowest SOD activity. Correlation analysis revealed significant correlations between SOD and inflammatory markers, organ injury markers, coagulation dysfunction indicators, nutritional markers, and lymphocytes counts. The ROC curve also showed good performance for the differentiation of severe cases and the prediction of death. Conclusion: SOD activity was significantly decreased in COVID-19 infected with Omicron variant and significantly correlated with systemic changes, and could be used as a biomarker to assess disease severity and predict mortality in COVID-19 clinical pathway management. Additionally, this finding will contribute to exploring new potential direction for the treatment of severe COVID-19 patients.

Greater upper limb muscle mass associated with reduced cardiovascular mortality compared with other muscle groups in diabetics.

OBJECTIVES: Although muscle mass and its distribution have been shown to affect prognosis, the association between regional muscle mass and cardiovascular mortality risk in diabetic patients remains unclear. METHODS: This prospective cohort study analyzed data from 2166 individuals with diabetes who participated in the National Health and Nutrition Survey conducted in the United States between 2003 to 2006 and 2011 to 2018, linked to the National Death Index. Weighted Kaplan-Meier analysis and multivariable Cox proportional hazards models were used to explore the association between different regional lean mass and cardiovascular mortality. RESULTS: The weighted Kaplan-Meier analysis revealed statistically significant differences in survival probabilities across lean upper limbs, lean lower limbs, lean gynoid, and lean trunk mass levels in diabetic participants (P < 0.05). In the multivariate adjusted Cox proportional hazards models, higher levels of upper limb lean mass were found to be associated with decreased cardiovascular mortality (hazard ratio, 0.589; 95% confidence interval, 0.332-0.976; P = 0.041). Notably, this correlation was more significant in men (hazard ratio, 0.378; 95% confidence interval, 0.171-0.834; P = 0.016), which was indicated by the results of the Cox regression and nonlinear regression analysis. CONCLUSIONS: Higher upper limb lean mass is associated with lower cardiovascular mortality compared with other regional lean mass in patients with diabetes, especially for men. Further research is needed to elucidate the mechanisms involved in muscle metabolic differentiation.

Endothelial dysfunction and disease severity in COVID-19: Insights from circulating Tang cell counts as a potential biomarker.

BACKGROUND AND AIM: Endothelial dysfunction is a common risk factor of severe COVID-19. Angiogenic T cells (Tang cells) play a critical role in repairing endothelial injury; however, their changes and potential roles in COVID-19 remain unclear. We aimed to assess Tang cell counts in patients with COVID-19 and evaluate their association with disease severity and prognosis. METHODS: Circulating Tang cell populations in patients with COVID-19 and healthy controls were quantified using flow cytometry. Demographic and routine laboratory data were recorded. RESULTS: The Tang cell count decreased significantly with increasing disease severity and were lowest in fatal cases. Additionally, the Tang cell count was significantly decreased in patients with comorbid cardiovascular disease or hypertension. Tang cell counts were negatively correlated with inflammatory markers, kidney and myocardial injury markers, coagulation dysfunction indicators, and viral load and positively correlated with oxidative stress markers, nutritional markers, and lymphocytes. Receiver operating characteristic curves confirmed that Tang cell count could serve as a potential biomarker for predicting disease severity and patient mortality. CONCLUSIONS: Circulating Tang cell count is significantly reduced in patients with COVID-19 and is correlated with disease severity and prognosis. The Tang cell count is an important potential biomarker for COVID-19 clinical management. Additionally, these findings provide insight into the pathological features of COVID-19 endothelial injury and provide new directions for treatment.

Development of a multiplex reverse transcription-quantitative PCR (qPCR) method for detecting common causative agents of swine viral diarrhea in China.

BACKGROUND: Diarrheal diseases caused by viral agents have led to a great morbidity, mortality, and economic loss in global pig industry. Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and group A porcine rotavirus (RVA) are main causative agents of swine viral diarrhea with similar clinical signs on Chinese farms and their co-infection is also common. However, it is still lack of a convenient method to detect these four agents. METHODS: A TaqMan multiplex qPCR method was developed to detect PEDV, TGEV, PDCoV, and RVA, simultaneously. This method was then applied to investigate 7,342 swine fecal samples or rectal swabs, as well as 1,246 swine intestinal samples collected from 2075 farms in China in 2022. RESULTS: Minimum detection limits of this method were 3 copies/µL for PEDV, 4 copies/µL for TGEV, 8 copies/µL for RVA, and 8 copies/µL for PDCoV, suggesting a good sensitivity. No signals were observed by using this method detecting other viral agents commonly prevalent in pigs, which is suggestive of a good specificity. Application of this method on investigating clinical samples demonstrated a relatively high positive rate for PEDV (22.21%, 1907/8588) and RVA (44.00%, 3779/8588). In addition, co-infection between PEDV and RVA was observed on 360 investigated farms, accounting for 17.35% (360/2075) of the farms where co-infection events were screened. CONCLUSIONS: A TaqMan multiplex qPCR method targeting PEDV, TGEV, PDCoV, and RVA was developed in this study. This method demonstrated a good specificity and sensitivity on investigating these four common viruses responsible for viral diarrhea on Chinese pig farms, which represents a convenient method for the monitoring and differential diagnosis of swine viral diarrhea.

Breaking the symmetry of cell contractility drives tubulogenesis via CXCL1 polarization.

The intricate interplay between biomechanical and biochemical pathways in modulating morphogenesis is an interesting research topic. How biomechanical force regulates epithelial cell tubulogenesis remains poorly understood. Here, we established a model of tubulogenesis by culturing renal proximal tubular epithelial cells on a collagen gel while manipulating contractile force. Epithelial cells were dynamically self-organized into tubule-like structures by augmentation of cell protrusions and cell-cell association. Reduction and asymmetric distribution of phosphorylated myosin light chain 2, the actomyosin contractility, in cells grown on soft matrix preceded tube connection. Notably, reducing matrix stiffness via sonication of collagen fibrils and inhibiting actomyosin contractility with blebbistatin promoted tubulogenesis, whereas inhibition of cytoskeleton polymerization suppressed it. CXC chemokine ligand 1 (CXCL1) expression was transcriptionally upregulated in cells undergoing tubulogenesis. Additionally, inhibiting actomyosin contractility facilitated CXCL1 polarization and cell protrusions preceding tube formation. Conversely, inhibiting the CXCL1-CXC receptor 1 pathway hindered cell protrusions and tubulogenesis. Mechanical property asymmetry with cell-collagen fibril interaction patterns at cell protrusions and along the tube structure supported the association of anisotropic contraction with tube formation. Furthermore, suppressing the mechanosensing machinery of integrin subunit beta 1 reduced CXCL1 expression, collagen remodeling, and impaired tubulogenesis. In summary, symmetry breaking of cell contractility on a soft collagen gel promotes CXCL1 polarization at cell protrusions which in turn facilitates cell-cell association and thus tubule connection.

Effects of Phenolic Evolution on Color Characteristics of Single-Cultivar Vitis vinifera L. Marselan and Merlot Wines during Vinification and Aging.

The loss of red hue in dry red wine has been a persistent issue for wine enterprises in western China. We investigated the changes in anthocyanins and non-anthocyanin phenols during the industrial-scale fermentation and one-year bottle aging of Vitis vinifera L. Merlot and Vitis vinifera L. Marselan, respectively, using the grapes in the Ningxia region. We also examined their correlation with color characterization. The study found that both anthocyanins and non-anthocyanin phenolics were rapidly extracted from grapes during alcohol fermentation. However, their concentrations decreased rapidly during malolactic fermentation. On the other hand, Vitisin A and Vitisin B were formed during alcoholic fermentation and decreased slowly from malolactic fermentation to storage period. Directly polymerized pigments (F-A and A-F), bridged polymerized pigments (A-e-F), and flavanyl-pyranoanthocyanins (A-v-F) from the reactions of anthocyanins (A) and flavan-3-ols (F), as well as pinotins were generated during the later stages of alcoholic fermentation, and remained at a high level throughout malolactic fermentation and bottle storage. Partial least squares regression and Pearson correlation analyses revealed that the red hue (a* value) of 'Merlot' and 'Marselan' wines was closely associated with monomeric anthocyanins and F-A type pigments. Furthermore, four pinotin components were positively correlated with the red hue (a* value) of 'Merlot' wine. These primary red components of the two varieties had a positive correlation with the level of flavan-3-ols. The data suggest that elevating the flavan-3-ol concentration during fermentation aids in improving the color stability of red wine.

Fecal PCR survey and genome analysis of Lawsonia intracellularis in China.

Proliferative enteropathy caused by Lawsonia intracellularis is an important economic associated disease to pig industry, but the knowledge about the prevalence of L. intracellularis in pig farms in China is limited. In addition, there is no complete genome sequence available for L. intracellularis isolates from China. In this study, we developed a TaqMan qPCR for the screening of L. intracellularis by targeting the bacterial 16S rDNA gene. Laboratory evaluations revealed a good sensitivity and specificity on detecting L. intracellularis nucleic acid. Using this method, we investigated 891 fecal samples from apparently healthy pigs in 47 farms. The results demonstrated a screening positive rate of 37.3% (95% CI, 34.1-40.5%) for the samples, and a farm screening positive rate of 93.6% (95% CI, 65.3-94.4%). The screening positive rate at herd level ranged from 6.67% (95% CI, 0.2-31.9%) to 40% (95% CI, 38-79.6%), while at animal level, the highest screening positive rate was found in 12-week-old pigs [85.7% (95% CI, 67.3-96.0%)]. Investigation of 705 diarrheal or bloody feces from symptomatic pigs revealed that the highest positive rate was found in replacement gilts which was 37.18% (95% CI, 45.1-89.5%). Secondly, we conducted the complete genome sequence of a L. intracellularis PPE-GX01-2022 from China through PacBio sequencing. The genome of PPE-GX01-2022 consisted of a chromosome of 1,439,110 bp in length and three plasmids of 193,063, 39,799, and 27,067 bp, respectively. This genome encoded 1,428 predicted proteins, 44 tRNAs, and 6 rRNAs. Sequence comparisons demonstrated that the genome sequence of PPE-GX01-2022 was highly homologous to those of two isolates from US, and these three isolates shared 1,378 core genes. The screening results suggest a high prevalence rate of L. intracellularis in Chinese pig farms. In addition, the genome sequence of the Chinese isolate was highly homologous to those of the field isolates from the US.

The fusion of multi-omics profile and multimodal EEG data contributes to the personalized diagnostic strategy for neurocognitive disorders.

BACKGROUND: The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and the lack of precise diagnostic methods and specific indicators. Developing personalized diagnostic strategies for NCDs has therefore become a priority. RESULTS: Multimodal electroencephalography (EEG) data of a matched cohort of normal aging (NA) and NCDs seniors were recorded, and their faecal samples and urine exosomes were collected to identify multi-omics signatures and metabolic pathways in NCDs by integrating metagenomics, proteomics, and metabolomics analysis. Additionally, experimental verification of multi-omics signatures was carried out in aged mice using faecal microbiota transplantation (FMT). We found that NCDs seniors had low EEG power spectral density and identified specific microbiota, including Ruminococcus gnavus, Enterocloster bolteae, Lachnoclostridium sp. YL 32, and metabolites, including L-tryptophan, L-glutamic acid, gamma-aminobutyric acid (GABA), and fatty acid esters of hydroxy fatty acids (FAHFAs), as well as disturbed biosynthesis of aromatic amino acids and TCA cycle dysfunction, validated in aged mice. Finally, we employed a support vector machine (SVM) algorithm to construct a machine learning model to classify NA and NCDs groups based on the fusion of EEG data and multi-omics profiles and the model demonstrated 92.69% accuracy in classifying NA and NCDs groups. CONCLUSIONS: Our study highlights the potential of multi-omics profiling and EEG data fusion in personalized diagnosis of NCDs, with the potential to improve diagnostic precision and provide insights into the underlying mechanisms of NCDs. Video Abstract.

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-ß activity through its receptor stability in dermal fibroblasts.

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.

CD248 Regulates Inflammation and Encapsulation in Silicone-Related Capsule Formation.

BACKGROUND: Capsular contracture is the most common reason for having a secondary breast implant operation. The failure of the implanted device and discomfort are related to foreign body response, which involves a pathologic encapsulation. An up-regulated expression of CD248 was previously demonstrated to modulate inflammation and fibrosis. The authors hypothesized that CD248 contributes to foreign body reaction and contracture during silicone-stimulated capsule formation. METHODS: A murine capsular contracture model was established to correlate CD248 with capsular contracture. The timing and site of CD248 expression were characterized by protein analysis and histologic examination. The capsules between wild-type mice and CD248 knockout mice were compared in this model to verify the possible role of CD248 in silicone-related capsule formation. RESULTS: CD248 was expressed in the peri-silicone implant capsule by stromal fibroblast and perivascular fibroblast. CD248 was overexpressed on day 4 and down to a constant level, but it was still up-regulated through day 21 to day 56 after silicone implantation. The CD248 knockout mice showed a prolonged inflammation period, whereas the wild-type mice developed a thinner but more collagenous capsule. CONCLUSIONS: In conclusion, an effective murine capsular contracture model was established to study the relationship between CD248 and capsular contracture. CD248 may play a role in inflammation and encapsulation during silicone implantation. CD248 deletion in mice contributed to a loose and irregular collagen bundle in a capsule area, implying a decrease in contracture. Therefore, CD248 could be a potential therapeutic target in capsular contracture. CLINICAL RELEVANCE STATEMENT: CD248 may play a role in inflammation and encapsulation during silicone implantation. It could be a potential therapeutic target in clinical capsular contracture.

Epidemiology of arrhythmogenic ventricular cardiomyopathy in China.

BACKGROUND: Arrhythmogenic ventricular cardiomyopathy (AVC) is a common cause of ventricular arrhythmias and mortality, but limited data are available from large Asian cohorts. Our aim was to explore the current status of AVC and second, we examined the prevalence of ventricular tachycardia (VT), heart failure (HF) and mortality in patients with AVC in the Chinese population. HYPOTHESIS: At present, some studies have reported that the incidence of AVC is on the rise, which may be due to the increasing number of diagnostic methods for AVC. However, there is no epidemiological data on AVC in the Chinese population, so we speculate that the incidence of AVC in the Chinese population is increasing. METHODS AND RESULTS: We studied 15 888 adults from the Beijing Municipal Health Commission Information Center (BMHCIC) registry database in China from January 2010 to December 2020, and calculated the average annual percentage change (AAPC). Second, we determined the incidence of VT, HF and mortality in patients with AVC. Of the 10 318 men and 5570 women who were screened by cardiac magnetic resonance or examined by myocardial biopsy, there were a total of 256 newly diagnosed AVC patients (mean [SD]: 37.54[17.10]; 39.45% female). The incidence of AVC increased from 7.60 (3.12-12.06) in 2010 to 19.62 (11.51-27.75) per 1000 person-years in 2020. Males had higher incidence of AVC than females. The AAPC for the rising incidence of AVC was 8.9 %. Males had similar VT prevalence (70.32% vs. 62.38%, p = 0.19) and mortality (1.94% vs. 1.98%, p = 0.98) but lower HF prevalence (42.58% vs. 60.40%, p = 0.006), when compared to females. Radiofrequency ablation (RFA) was more likely to be performed in males (p = 0.006). CONCLUSIONS: The rising trend in AVC incidence was evident, with two-fold increase by 2020. Males with AVC had similar VT prevalence and mortality rate, but HF prevalence were lower than females, perhaps impacted by RFA use.

CD248 promotes insulin resistance by binding to the insulin receptor and dampening its insulin-induced autophosphorylation.

BACKGROUND: In spite of new treatments, the incidence of type 2 diabetes (T2D) and its morbidities continue to rise. The key feature of T2D is resistance of adipose tissue and other organs to insulin. Approaches to overcome insulin resistance are limited due to a poor understanding of the mechanisms and inaccessibility of drugs to relevant intracellular targets. We previously showed in mice and humans that CD248, a pre/adipocyte cell surface glycoprotein, acts as an adipose tissue sensor that mediates the transition from healthy to unhealthy adipose, thus promoting insulin resistance. METHODS: Molecular mechanisms by which CD248 regulates insulin signaling were explored using in vivo insulin clamp studies and biochemical analyses of cells/tissues from CD248 knockout (KO) and wild-type (WT) mice with diet-induced insulin resistance. Findings were validated with human adipose tissue specimens. FINDINGS: Genetic deletion of CD248 in mice, overcame diet-induced insulin resistance with improvements in glucose uptake and lipolysis in white adipose tissue depots, effects paralleled by increased adipose/adipocyte GLUT4, phosphorylated AKT and GSK3ß, and reduced ATGL. The insulin resistance of the WT mice could be attributed to direct interaction of the extracellular domains of CD248 and the insulin receptor (IR), with CD248 acting to block insulin binding to the IR. This resulted in dampened insulin-mediated autophosphorylation of the IR, with reduced downstream signaling/activation of intracellular events necessary for glucose and lipid homeostasis. INTERPRETATION: Our discovery of a cell-surface CD248-IR complex that is accessible to pharmacologic intervention, opens research avenues toward development of new agents to prevent/reverse insulin resistance. FUNDING: Funded by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundations for Innovation (CFI), the Swedish Diabetes Foundation, Family Ernfors Foundation and Novo Nordisk Foundation.

DOTA functionalized adsorbent DOTA@Sludge@Chitosan derived from recycled shrimp shells and sludge and its application for lead and chromium removal from water.

DOTA@Sludge@Chitosan was synthesized by a facile treatment using DOTA (1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid) to modify dry sludge and chitosan in an acidic solution. The performance of developed DOTA@Sludge@Chitosan was investigated for the adsorptive removal of Cr6+ and Pb2+ from water. Characterization studies showed that the materials possess a large surface area (52.009 m2/g), pore volume (0.069 cm3/g), and abundant functional groups of amino and hydroxyl. The prepared material showed a synergetic effect due to carboxylic acid and sludge, effectively removing Cr6+ and Pb2+. It reached 329.4 mg/g (Pb2+) and 273.3 mg/g (Cr6+) at 20 °C, much higher than commercial activated carbon. The regeneration of the adsorbent was tested for six adsorption and desorption cycles. The results demonstrate that the DOTA@Sludge@Chitosan adsorbent well-maintained high adsorption capacity attributed to its stability, making it a promising adsorbent for heavy metals removal from industrial effluent.

Genetic screening of 15 hearing loss variants in 77,647 neonates with clinical follow-up.

BACKGROUND: To analyze the genotype distribution and frequency of hearing loss genes in newborn population and evaluate the clinical value of genetic screening policy in China. METHODS: Genetic screening for hearing loss was offered to 84,029 neonates between March 2019 and December 2021, of whom 77,647 newborns accepted the screening program with one-year follow-up. The genotyping of 15 hot spot variants in GJB2, GJB3, SLC26A4, and MT-RNR1 was performed on microarray platform. RESULTS: A total of 3.05% (2369/77,647) newborns carried at least one genetic hearing loss-associated variant, indicated for early preventive management. The carrier frequency of GJB2 gene was the highest, at 1.48% (1147/77,647), followed by SLC26A4 gene at 1.07% (831/77,647), and GJB3 gene at 0.23% (181/77,647). GJB2 c.235delC variant and SLC26A4 IVS7-2A>G variant were the most common allelic variants with allele frequency of 0.6304% (979/155,294) and 0.3992% (620/155,294), respectively. 10 children are identified as homozygous or compound heterozygous for pathogenic variants (4 in GJB2, 6 in SLC26A4), and 7 of these infants had passed the hearing screening. Following up of the genetically screened newborns revealed that genetic screening detected more hearing-impaired infants than hearing screening alone. Genetic screening helped identify the infants who had passed the initial hearing screening, and reduced time for diagnosis and intervention of hearing aid. In addition, we identified 234 newborns (0.30%, 234/77,647) susceptible to preventable aminoglycoside antibiotic ototoxicity undetectable by hearing screening. CONCLUSION: We performed the largest-scale neonatal carrier screening for hearing loss genes in Southeast China. Our results indicated that genetic screening is an important complementation to conventional hearing screening. Our practice and experience may facilitate the application and development of neonatal genetic screening policy in mainland China.

Analyzing the correlation between quinolone-resistant Escherichia coli resistance rates and climate factors: A comprehensive analysis across 31 Chinese provinces.

BACKGROUND: The increasing problem of bacterial resistance, particularly with quinolone-resistant Escherichia coli (QnR eco) poses a serious global health issue. METHODS: We collected data on QnR eco resistance rates and detection frequencies from 2014 to 2021 via the China Antimicrobial Resistance Surveillance System, complemented by meteorological and socioeconomic data from the China Statistical Yearbook and the China Meteorological Data Service Centre (CMDC). Comprehensive nonparametric testing and multivariate regression models were used in the analysis. RESULT: Our analysis revealed significant regional differences in QnR eco resistance and detection rates across China. Along the Hu Huanyong Line, resistance rates varied markedly: 49.35 in the northwest, 54.40 on the line, and 52.30 in the southeast (P = 0.001). Detection rates also showed significant geographical variation, with notable differences between regions (P < 0.001). Climate types influenced these rates, with significant variability observed across different climates (P < 0.001). Our predictive model for resistance rates, integrating climate and healthcare factors, explained 64.1% of the variance (adjusted R-squared = 0.641). For detection rates, the model accounted for 19.2% of the variance, highlighting the impact of environmental and healthcare influences. CONCLUSION: The study found higher resistance rates in warmer, monsoon climates and areas with more public health facilities, but lower rates in cooler, mountainous, or continental climates with more rainfall. This highlights the strong impact of climate on antibiotic resistance. Meanwhile, the predictive model effectively forecasts these resistance rates using China's diverse climate data. This is crucial for public health strategies and helps policymakers and healthcare practitioners tailor their approaches to antibiotic resistance based on local environmental conditions. These insights emphasize the importance of considering regional climates in managing antibiotic resistance.