Ancestral Origins and Admixture History of Kazakhs.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin, genomic makeup, and genetic interaction with surrounding populations are not well understood. To decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from 4 ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from the Uyghurs in terms of their overall genomic makeup, although the 2 populations were closely related in genetics, and both showed a substantial admixture of western and eastern peoples. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those living or along the old Silk Road.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Longitudinal Immune Profiling Highlights CD4+ T Cell Exhaustion Correlated with Liver Fibrosis in Schistosoma japonicum Infection.

Schistosomiasis remains an important public health concern. The eggs deposited in livers invoke a Th2-dominant response, which mediates the fibrotic granulomatous response. However, the mechanisms involved in this immunopathological process are still not perfectly clear. Here, we report a single-cell transcriptional landscape of longitudinally collected BALB/c mouse splenocytes at different time points after Schistosoma japonicum infection. We found that exhausted CD4+ T cells were enriched after infection, changing from coproducing multiple cytokines to predominantly producing the Th2 cytokine IL-4. Regulatory B cells had high expression of Fcrl5, Ptpn22, and Lgals1, potentially regulating exhausted CD4+ T cells via direct PD-1-PD-L2 and PD-1-PD-L1 interactions. Within the myeloid compartment, the number of precursor and immature neutrophils sharply increased after infection. Moreover, dendritic cells, macrophages, and basophils showed inhibitory interactions with exhausted CD4+ T cells. Besides, in mouse livers, we found that exhausted CD4+ T cells were distributed around egg granuloma, promoting collagen expression in primary mouse hepatic stellate cells via IL-4 secretion, resulting in liver fibrosis. Our study provides comprehensive characterization of the composition and cellular states of immune cells with disease progression, which will facilitate better understanding of the mechanism underlying liver fibrotic granulomatous response in schistosomiasis.

High-Performance Up-Conversion Photodetectors with Zero-Barrier Interconnection via Self-Assembled Surface Dipoles.

The performance of lead sulfide (PbS) quantum-dot-based up-conversion photodetectors is greatly limited owing to a large potential barrier at the interconnection layer between the photodetecting (PD) unit and light-emitting (LED) unit. Thus, very high driving voltage is required, rendering high energy consumption and poor working stability. By introducing azetidinium iodide (AzI) at the PD/LED interface, zero-barrier interconnection was achieved for the PbS-based infrared up-conversion photodetectors. The turn-on voltage under infrared illumination was greatly reduced to 1.2 V and a high photon-to-photon conversion efficiency (ηpp) of ∼3% was obtained at 3 V, showing a 10-fold enhancement compared to those previously reported devices. The mechanism for the regulation of interface energy level alignments was related to the self-assembly of the AzI dipole molecules, resulting from the van der Waals force between the S atoms in the ligands of PbS and the protonated H atoms around N atoms in AzI.

Fluorogenic Peptide Sensor Array Derived from Angiotensin-Converting Enzyme 2 Classifies Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.

Genetic Origins and Adaptive Evolution of the Deng People on the Tibetan Plateau.

The Tibetan Plateau is populated by diverse ethnic groups, but most of them are underrepresented in genomics studies compared with the Tibetans (TIB). Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30-60×) and analyzed the data together with that of TIB and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700-7,200 years) was more recent than that between highlanders and the Han Chinese (Deng-HAN, ∼9,000-14,000 years; TIB-HAN, 7,200-10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the TIB like HLA-DQB1, whereas others like KLHL12 were not reported in TIB. In contrast, the top candidate genes harboring AGVs as previously identified in TIB, like EPAS1 and EGLN1, do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the TIB. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau.

Polar Covalent Triazine Frameworks as High-Performance Potassium Metal Battery Cathodes.

The exploration of potassium metal batteries (PMBs) has been intensified, leveraging potassium's abundant availability, low redox potential, and small Stokes radius. Covalent triazine frameworks (CTFs) stand out for their accessible nitrogen sites and customizable structures, making them attractive electrode materials. Nonetheless, there is a lack of established design principles to guide the development of high-performance PMBs using CTFs. In this work, CTFs consisting of different monomers are used as PMB cathodes to investigate the structure-performance correlation. The electronic structure analysis reveals the polar characteristic of a CTF derived from the tetracyanoquinodimethane monomer, setting it apart with superior capacity (161 mAh g-1 at 0.1 A g-1), rate performance (85 mAh g-1 at 5 A g-1), and stability (capacity retention of 81% after 1000 cycles) over three non-polar counterparts in PMBs. Calculations based on density functional theory support the exceptional performance with increased K+ adsorption energy. Ultimately, among multifaceted factors, the polarity of CTF is the leading element that determines the K+ storage capability. These findings pave the way for the development of prudent CTF electrodes for high-performance PMBs.

Broad-spectrum vaccine via combined immunization routes triggers potent immunity to SARS-CoV-2 and its variants.

IMPORTANCE: The development of broad-spectrum SARS-CoV-2 vaccines will reduce the global economic and public health stress from the COVID-19 pandemic. The use of conserved T-cell epitopes in combination with spike antigen that induce humoral and cellular immune responses simultaneously may be a promising strategy to further enhance the broad spectrum of COVID-19 vaccine candidates. Moreover, this research suggests that the combined vaccination strategies have the ability to induce both effective systemic and mucosal immunity, which may represent promising strategies for maximizing the protective efficacy of respiratory virus vaccines.

Essential role of pyrophosphate homeostasis mediated by the pyrophosphate-dependent phosphofructokinase in Toxoplasma gondii.

Many biosynthetic pathways produce pyrophosphate (PPi) as a by-product, which is cytotoxic if accumulated at high levels. Pyrophosphatases play pivotal roles in PPi detoxification by converting PPi to inorganic phosphate. A number of apicomplexan parasites, including Toxoplasma gondii and Cryptosporidium parvum, express a PPi-dependent phosphofructokinase (PPi-PFK) that consumes PPi to power the phosphorylation of fructose-6-phosphate. However, the physiological roles of PPi-PFKs in these organisms are not known. Here, we report that Toxoplasma expresses both ATP- and PPi-dependent phosphofructokinases in the cytoplasm. Nonetheless, only PPi-PFK was indispensable for parasite growth, whereas the deletion of ATP-PFK did not affect parasite proliferation or virulence. The conditional depletion of PPi-PFK completely arrested parasite growth, but it did not affect the ATP level and only modestly reduced the flux of central carbon metabolism. However, PPi-PFK depletion caused a significant increase in cellular PPi and decreased the rates of nascent protein synthesis. The expression of a cytosolic pyrophosphatase in the PPi-PFK depletion mutant reduced its PPi level and increased the protein synthesis rate, therefore partially rescuing its growth. These results suggest that PPi-PFK has a major role in maintaining pyrophosphate homeostasis in T. gondii. This role may allow PPi-PFK to fine-tune the balance of catabolism and anabolism and maximize the utilization efficiency for carbon nutrients derived from host cells, increasing the success of parasitism. Moreover, PPi-PFK is essential for parasite propagation and virulence in vivo but it is not present in human hosts, making it a potential drug target to combat toxoplasmosis.

Two apicoplast dwelling glycolytic enzymes provide key substrates for metabolic pathways in the apicoplast and are critical for Toxoplasma growth.

Many apicomplexan parasites harbor a non-photosynthetic plastid called the apicoplast, which hosts important metabolic pathways like the methylerythritol 4-phosphate (MEP) pathway that synthesizes isoprenoid precursors. Yet many details in apicoplast metabolism are not well understood. In this study, we examined the physiological roles of four glycolytic enzymes in the apicoplast of Toxoplasma gondii. Many glycolytic enzymes in T. gondii have two or more isoforms. Endogenous tagging each of these enzymes found that four of them were localized to the apicoplast, including pyruvate kinase2 (PYK2), phosphoglycerate kinase 2 (PGK2), triosephosphate isomerase 2 (TPI2) and phosphoglyceraldehyde dehydrogenase 2 (GAPDH2). The ATP generating enzymes PYK2 and PGK2 were thought to be the main energy source of the apicoplast. Surprisingly, deleting PYK2 and PGK2 individually or simultaneously did not cause major defects on parasite growth or virulence. In contrast, TPI2 and GAPDH2 are critical for tachyzoite proliferation. Conditional depletion of TPI2 caused significant reduction in the levels of MEP pathway intermediates and led to parasite growth arrest. Reconstitution of another isoprenoid precursor synthesis pathway called the mevalonate pathway in the TPI2 depletion mutant partially rescued its growth defects. Similarly, knocking down the GAPDH2 enzyme that produces NADPH also reduced isoprenoid precursor synthesis through the MEP pathway and inhibited parasite proliferation. In addition, it reduced de novo fatty acid synthesis in the apicoplast. Together, these data suggest a model that the apicoplast dwelling TPI2 provides carbon source for the synthesis of isoprenoid precursor, whereas GAPDH2 supplies reducing power for pathways like MEP, fatty acid synthesis and ferredoxin redox system in T. gondii. As such, both enzymes are critical for parasite growth and serve as potential targets for anti-toxoplasmic intervention designs. On the other hand, the dispensability of PYK2 and PGK2 suggest additional sources for energy in the apicoplast, which deserves further investigation.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Scoparone inhibits the development of hepatocellular carcinoma by modulating the p38 MAPK/Akt/NF-κB signaling in nonalcoholic fatty liver disease mice.

BACKGROUND AND STUDY AIM: The mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) into hepatocellular carcinoma (HCC) remains confusing and the therapeutics approaches are also challenging. Here, we aimed to investigate the effects of scoparone on the treatment of HCC stemmed from NAFLD and the underlying mechanisms. MATERIALS AND METHODS: A model of NAFLD-HCC was created in mice, and these mice were treated with scoparone. Biochemical assays were conducted to assess the levels of biochemical markers. Tumors were evaluated through morphological examination. Histopathological analyses were performed using oil red O, Hematoxylin and Eosin, and Masson coloration assays. Immunohistochemistry (IHC) and RT-PCR were performed to analyze protein expression and measure mRNA expression levels, respectively. RESULTS: Scoparone could ameliorate the pathological alterations observed in NAFLD-HCC mouse model. IHC analysis indicated an upregulation of NF-κB p65 expression in both NAFLD and NAFLD-HCC models, which was subsequently reverted by scoparone administration. Furthermore, scoparone treatment resulted in a reversal of the increased mRNA expression levels of NF-κB target genes, including TNF-α, MCP-1, iNOS, COX-2, NF-κB, and MMP-9, which were originally elevated in the NAFLD-HCC condition. Additionally, scoparone exhibited a capacity to counteract the activation of the MAPK/Akt signaling in the NAFLD-HCC model. CONCLUSION: These findings suggest that scoparone holds promise as a potential therapeutic agent for NAFLD-associated HCC, and its model of action may involve the regulation of inflammatory pathways governed by the MAPK/Akt/NF-κB signaling cascade.

The value of bioimpedance analysis in the assessment of hydration and nutritional status in children on chronic peritoneal dialysis.

Bioimpedance analysis (BIA)-body composition monitoring (BCM) has been used to evaluate the hydration and nutritional status of adults and children on dialysis. However, its clinical application still has challenges, so further exploration is valuable. We used BIA-BCM to evaluate the hydration and nutritional status of children undergoing chronic peritoneal dialysis from 1 July 2021 to 31 December 2022 in the Children's Hospital of Fudan University to explore the clinical value of this method. A total of 84 children on chronic peritoneal dialysis (PD) were included. In the PD group, 16 (19.05%) and 31 (36.90%) had mild and severe overhydration (OH), respectively; 41.27% (26/63) had a low lean tissue index (LTI). In the PD group, patients with relative OH (Re-OH) > 5.6% had significantly higher systolic blood pressure (SBP) and SBP z score (SBPz). Patients with LTI > 12% had significantly higher body mass index (BMI) and BMI z score (BMIz). Canonical correlation analysis indicated a linear relationship (ρ = 0.708) between BIA-BCM hydration and the clinical hydration indicator and a linear relationship (ρ = 0.995) between the BIA-BCM nutritional indicator and the clinical nutritional indicator. A total of 56% of children on chronic peritoneal dialysis had OH, and 41% had a low LTI. In PD patients, SBP and SBPz were correlated with BIA-BCM Re-OH, and BMI and BMIz were correlated with BIA-BCM LTI. BIA-BCM indicators have good clinical value in evaluating hydration and nutrition.

Craig-Hückel Hybrid Aromatic Metalla-dehydro[11]annulenes Constructed by a Formal [10+1] Cycloaddition Reaction.

Aromatic metalla-annulenes are important aromatic compounds, research into which has been mainly concentrated on metal-benzenes and their lower homologues. Reports on their superior homologs are rare, and this has greatly limited the systematic study of their properties. In this work, a series of osma-dehydro[11]annulenes with good air and thermal stability were prepared in high yields through a simple [10+1] strategy, by incorporating a metal fragment into conjugated ten-carbon chains in a one-pot reaction. They are the first monometallic aromatic metalla-[n]annulenes with the ring size larger than 6, and their Craig-Hückel hybrid aromaticity is supported by various physical and computational parameters. Besides, these complexes show versatile reactivities, not only giving further evidence for their aromaticity, but also demonstrating their physical and chemical properties can easily be regulated. This work enriches the metalla-aromatic chemistry, and provides a new avenue for the synthesis of large metalla-annulenes with different ring sizes.

Biomass-Derived Bifunctional Cathode Electrocatalyst and Multiadaptive Gel Electrolyte for High-Performance Flexible Zn-Air Batteries in Wide Temperature Range.

High-efficiency and low-cost bifunctional electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), as well as gel electrolytes with high thermal and mechanical adaptability are required for the development of flexible batteries. Herein, abundant Setaria Viridis (SV) biomass is selected as the precursor to prepare porous N-doped carbon tubes with high specific surface area and the 900 °C calcination product of SV (SV-900) shows the optimum ORR/OER activities with a small EOER -EORR of 0.734 V. Meanwhile, a new multifunctional gel electrolyte named C20E2G5 is prepared using cellulose extracted from another widely distributed biomass named flax as the skeleton, epichlorohydrin as the cross-linker and glycerol as the antifreezing agent. C20E2G5 possesses high ionic conductivity from -40 to + 60 °C, excellent tensile and compressive resistance, high adhesion, strong freezing and heat resistance. Moreover, the symmetrical cell assembled with C20E2G5 can significantly inhibit Zn dendrite growth. Finally, flexible solid-state Zn-air batteries assembled with SV-900 and C20E2G5 show high open circuit voltage, large energy density, and long-term operation stability between -40 and + 60 °C. This biomass-based approach is generic and can be used for the development of diverse next-generation electrochemical energy conversion and storage devices.

Idiopathic hypogonadotropic hypogonadism caused by compound heterozygosity for two novel mutations in the GNRH1 gene: a case report.

BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare congenital or acquired genetic disorder caused by gonadotropin-releasing hormone (GnRH) deficiency. IHH patients are divided into two major groups, hyposmic or anosmic IHH (Kallmann syndrome) and normosmic IHH (nIHH), according to whether their sense of smell is intact. Here we report a case of novel compound heterozygous mutations in the GNRH1 gene in a 15-year-old male with nIHH. CASE PRESENTATION: The patient presented typical clinical symptoms of delayed testicular development, with testosterone < 3.5 mmol/L and reduced gonadotropin (follicle-stimulating hormone, luteinizing hormone) levels. Two heterozygous variants of the GNRH1 gene were detected, nonsense variant 1: c.85G > T:p.G29* and variant 2: c.1A > G:p.M1V, which disrupted the start codon. CONCLUSIONS: Two GNRH1 mutations responsible for nIHH are identified in this study. Our findings extend the mutational spectrum of GNRH1 by revealing novel causative mutations of nIHH.

Study on the correlation between bioelectrical impedance analysis index and protein energy consumption in maintenance dialysis patients.

BACKGROUND: Protein-energy wasting (PEW) has been reported to be pretty common in maintenance dialysis patients. However, the existing PEW diagnostic standard is limited in clinical use due to the complexity of it. Bioelectrical impedance analysis (BIA), as a non-invasive nutritional assessment method, can objectively and quantitatively analyze the changes of body tissue components under different nutritional states. We aim to explore the association between PEW and BIA and establish a reliable diagnostic model of PEW. METHODS: We collected cross-sectional data of 609 maintenance dialysis patients at the First Affiliated Hospital, College of Medicine, Zhejiang University. PEW was diagnosed according to International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Among them, 448 consecutive patients were included in the training set for the establishment of a diagnostic nomogram. 161 consecutive patients were included for internal validation. 52 patients from Zhejiang Hospital were included for external validation of the diagnostic model. Correlation analysis of BIA indexes with other nutritional indicators was performed. Logistic regression was used to examine the association of BIA indexes with PEW. 12 diagnostic models of PEW in maintenance dialysis patients were developed and the performance of them in terms of discrimination and calibration was evaluated using C statistics and Hosmer-Lemeshow-type χ2 statistics. After comparing to existing diagnostic models, and performing both internal and external validation, we finally established a simple but reliable PEW diagnostic model which may have great value of clinical application. RESULTS: A total of 609 individuals from First Affiliated Hospital, College of Medicine, Zhejiang University and 52 individuals from Zhejiang Hospital were included. After full adjustment, age, peritoneal dialysis (compared to hemodialysis), subjective global assessment (SGA, compared to non-SGA) and water ratio were independent risk factors, while triglyceride, urea nitrogen, calcium, ferritin, BCM, VFA and phase angle were independent protective factors of PEW. The model incorporated water ratio, VFA, BCM, phase angle and cholesterol revealed best performance. A nomogram was developed according to the results of model performance. The model achieved high C-indexes of 0.843 in the training set, 0.841 and 0.829 in the internal and external validation sets, respectively, and had a well-fitted calibration curve. The net reclassification improvement (NRI) showed 8%, 13%, 2%, 38%, 36% improvement of diagnostic accuracy of our model compared with "PEW score model", "modified PEW score model", "3-index model", "SGA model" and "BIA decision tree model", respectively. CONCLUSIONS: BIA can be used as an auxiliary tool to evaluate PEW risk and may have certain clinical application value.

Formation of a D-shaped optical fiber by in-cavity online polishing for high resolution sensing in a chaotic correlation fiber loop ring down system.

Online monitoring of the polishing process of a D-shaped optical fiber sensor is performed in this paper by means of a chaotic correlation fiber loop ring down (CCFLRD) system. The ring down time of the autocorrelation coefficient decreases with the increase in polishing loss caused by different mesh sizes. A comparison of the sensitivity and resolution of the CCFLRD system with different polishing losses in the length of a fiber loop cavity are carried out. Online polishing in the fiber loop cavity with a very short length is proposed and demonstrated using different polishing mesh numbers to increase the sensitivity and resolution of the system. A high sensitivity of 31.871n s -1 R I U -1 and resolution of 10-4 R I U for refractive index sensing in the range of 1.3347-1.3721 correspond to different concentrations of sodium chloride.

Platelet-rich Plasma Promotes Restoration of the Anterior Vaginal Wall for the Treatment of Pelvic Floor Dysfunction in Rats.

STUDY OBJECTIVE: To determine the efficacy of using platelet-rich plasma (PRP) for vaginal wall repair in rats with vaginal wall impairment induced by vaginal distension (VD). DESIGN: A single-blind, randomized study. SETTING: A certified animal research facility. ANIMALS: Twenty-four female Sprague Dawley rats. INTERVENTIONS: Female Sprague Dawley rats were divided into sham (n = 8), VD (n = 8), and VD + PRP (n = 8) groups. Vaginal tissues from the VD group were dissected at 28-day post injury. VD + PRP rats received vaginal PRP injections on the 1st, 7th, 14th, and 21st day after VD and sacrificed on the 28th day. MEASUREMENTS AND MAIN RESULTS: Urodynamic tests were performed in all rats. Immunohistochemistry was used to evaluate matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9). Masson's staining was used to evaluate collagen fibers and calculate collagen volume fraction. Collagen fiber damage was confirmed in the VD group, evidenced by thinner and sparse distribution of collagen fibers, with significantly higher MMP-2 and MMP-9 expression than the sham group (p <.05). The collagen fiber damage in the vaginal wall likely led to pelvic floor dysfunction (PFD), evidenced by significantly decreased bladder leak-point pressure (p <.01) and abdominal leak-point pressure (p <.01) in the VD group compared with the sham group. After completion of the PRP treatment, a significantly higher collagen volume fraction (p <.01) and significantly increased bladder leak-point pressure (p <.05) and abdominal leak-point pressure (p <.01) were achieved in the VD + PRP compared with the VD group, thus indicating repair of the vaginal wall and improvement of PFD. CONCLUSION: PRP injections facilitate the regeneration of vaginal wall tissue, particularly collagen fiber, after VD, leading to functional improvement of PFD. Findings support the feasibility of using PRP as a novel treatment for PFD.

Isolation, identification, and preparation of tyrosinase inhibitory peptides from Pinctada martensii meat.

Recently, natural tyrosinase inhibitors have gained attention in clinical cosmetology research. In this study, the enzymatic hydrolysis of Pinctada martensii meat by protease from Bacillus licheniformis, 401 peptides with tyrosinase inhibitory were identified after isolated by ultrafiltration and Sephadex G-15 from the fraction F4. The peptide effects on the tyrosinase activity and structure were evaluated using molecular docking. Three synthetic peptides classified as W1 (WDRPKDDGGSPIK), W2 (DRGYPPVMF), and W3 (SGGGGGGGLGSGGSIRSSY), which had the lowest binding energies were selected for in vitro synthesis and biological activity investigation. The W3 peptide (5 mg/mL) had the highest tyrosinase activity, SPF, DPPH, and ABTS clearance values, and total antioxidant capacity. W3 did not affect the survival rate of mouse melanoma B16-F10 cells (1.0-5.0 mg/mL) but decreased the melanin content. Hence, W3 could be suitable for multifunctional tyrosinase inhibition and provides a novel method to use marine organisms as natural tyrosinase inhibitor sources.