Auditory and speech outcomes of cochlear implantation in patients with Waardenburg syndrome: a meta-analysis.

Objective: This study aims to assess the potential efficacy of cochlear implantation as a treatment for patients with Waardenburg syndrome (WS) and to guide clinical work by comparing the effect of auditory and speech recovery after cochlear implantation in patients with WS and non-WS. Methods: PubMed, the Cochrane Library, CNKI, and Wanfang Data were sources for retrieving literature on cochlear implantation in WS, and clinical data meeting the inclusion criteria were meta-analyzed using RevMan5.41. Results: A total of nine articles were included in this study, including 132 patients with WS and 815 patients in the control group. Meta-analysis showed that there are no significant differences in the scores for categories of audit performance (CAP), speech intelligibility rating (SIR), and parents' evaluation of aural/oral performance of children (PEACH) between the WS group and the control group. Conclusion: Cochlear implantation demonstrates comparable auditory and speech recovery outcomes for WS patients and non-WS patients.

StripeRust-Pocket: A Mobile-Based Deep Learning Application for Efficient Disease Severity Assessment of Wheat Stripe Rust.

Wheat stripe rust poses a marked threat to global wheat production. Accurate and effective disease severity assessments are crucial for disease resistance breeding and timely management of field diseases. In this study, we propose a practical solution using mobile-based deep learning and model-assisted labeling. StripeRust-Pocket, a user-friendly mobile application developed based on deep learning models, accurately quantifies disease severity in wheat stripe rust leaf images, even under complex backgrounds. Additionally, StripeRust-Pocket facilitates image acquisition, result storage, organization, and sharing. The underlying model employed by StripeRust-Pocket, called StripeRustNet, is a balanced lightweight 2-stage model. The first stage utilizes MobileNetV2-DeepLabV3+ for leaf segmentation, followed by ResNet50-DeepLabV3+ in the second stage for lesion segmentation. Disease severity is estimated by calculating the ratio of the lesion pixel area to the leaf pixel area. StripeRustNet achieves 98.65% mean intersection over union (MIoU) for leaf segmentation and 86.08% MIoU for lesion segmentation. Validation using an additional 100 field images demonstrated a mean correlation of over 0.964 with 3 expert visual scores. To address the challenges in manual labeling, we introduce a 2-stage labeling pipeline that combines model-assisted labeling, manual correction, and spatial complementarity. We apply this pipeline to our self-collected dataset, reducing the annotation time from 20 min to 3 min per image. Our method provides an efficient and practical solution for wheat stripe rust severity assessments, empowering wheat breeders and pathologists to implement timely disease management. It also demonstrates how to address the "last mile" challenge of applying computer vision technology to plant phenomics.

G-Protein Coupled Receptor 1 Is Involved in Tetrachlorobisphenol A-Induced Inflammatory Response in Jurkat Cells.

Estrogens can affect the immune inflammatory response through estrogen receptor alpha (ERα), but the specific role of estrogen member receptor G-protein coupled receptor 1 (GPER1) in this process remains unclear. In this study, we evaluated the effects of tetrachlorobisphenol A (TCBPA), which has estrogen activity, on immune inflammatory-related indicators of Jurkat cells, as well as investigated the role of GPER1 in these effects. The results showed that TCBPA at lower concentrations significantly promoted the viability of Jurkat cells, whereas higher concentrations decreased cell viability. TCBPA at concentrations ranging from 1 to 25 µM increased the intracellular reactive oxygen species (ROS) levels. Additionally, treatment with 10 µM TCBPA increased the protein expression of ERα and GPER1, elevated the phosphorylation of protein kinase B (p-Akt), and upregulated the mRNA levels of GPER1, Akt, and phosphoinositide 3-kinase (PI3K) genes. Treatment with 10 µM TCBPA also upregulated the protein or gene expression of pro-inflammatory cytokines, such as interleukins (IL1ß, IL2, IL6, IL8, IL12α) and tumor necrosis factor alpha (TNFα) in Jurkat cells. Furthermore, pretreatment with a GPER1 inhibitor G15 significantly reduced the mRNA levels of Akt induced by 10 µM TCBPA. Moreover, the upregulation of mRNA expression of RelA (p65), TNFα, IL6, IL8, and IL12α induced by 10 µM TCBPA was also significantly attenuated after G15 pretreatment. These findings suggest that TCBPA upregulates the expression of genes related to inflammatory responses by activating the GPER1-mediated PI3K/Akt signaling pathway. This study provides new insights into the mechanism of TCBPA-induced inflammatory response.

Degradation of perineuronal nets in the medial prefrontal cortex promotes extinction and reduces reinstatement of methamphetamine-induced conditioned place preference in female mice.

The high rate of relapse to compulsive methamphetamine (MA)-taking and seeking behaviors after abstinence constitutes a major obstacle to the treatment of MA addiction. Perineuronal nets (PNNs), essential components of the extracellular matrix, play a critical role in synaptic function, learning, and memory. Abnormalities in PNNs have been closely linked to a series of neurological diseases, such as addiction. However, the exact role of PNNs in MA-induced related behaviors remains elusive. Here, we established a MA-induced conditioned place preference (CPP) paradigm in female mice and found that the number and average optical density of PNNs increased significantly in the medial prefrontal cortex (mPFC) of mice during the acquisition, extinction, and reinstatement stages of CPP. Notably, the removal of PNNs in the mPFC via chondroitinase ABC (ChABC) before extinction training not only facilitated the extinction of MA-induced CPP and attenuated the relapse of extinguished MA preference but also significantly reduced the activation of c-Fos in the mPFC. Similarly, the ablation of PNNs in the mPFC before reinstatement markedly lessened the reinstatement of MA-induced CPP, which was accompanied by the decreased expression of c-Fos in the mPFC. Collectively, our results provide more evidence for the implication of degradation of PNNs in facilitating extinction and preventing relapse of MA-induced CPP, which indicate that targeting PNNs may be an effective therapeutic option for MA-induced CPP memories.

Oral edaravone ameliorates behavioral deficits and pathologies in a valproic acid-induced rat model of autism spectrum disorder.

Autism spectrum disorder (ASD) is neurodevelopmental disorder with a high incidence rate, characterized by social deficits and repetitive behaviors. There is currently no effective management available to treat the core symptoms of ASD; however, oxidative stress has been implicated in its pathogenesis. Edaravone (EDA), a free-radical scavenger, is used to treat amyotrophic lateral sclerosis (ALS) and acute ischemic stroke (AIS). Here, we hypothesized that an oral formula of EDA may have therapeutic efficacy in the treatment of core ASD symptoms. A rat model of autism was established by prenatal exposure to valproic acid (VPA), and the offsprings were orally treated with EDA at low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg) doses once daily for 28 days starting from postnatal day 25 (PND25). Oral EDA administration alleviated the core symptoms in VPA rats in a dose-dependent manner, including repetitive stereotypical behaviors and impaired social interaction. Furthermore, oral administration of EDA significantly reduced oxidative stress in a dose-dependent manner, as evidenced by a reduction in oxidative stress markers and an increase in antioxidants in the blood and brain. In addition, oral EDA significantly attenuated downstream pathologies, including synaptic and mitochondrial damage in the brain. Proteomic analysis further revealed that EDA corrected the imbalance in brain oxidative reduction and mitochondrial proteins induced by prenatal VPA administration. Overall, these findings demonstrate that oral EDA has therapeutic potential for ASD by targeting the oxidative stress pathway of disease pathogenesis and paves the way towards clinical studies.

Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155.

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

Photoinduced decarboxylative germylation of α-fluoroacrylic acids: access to germylated monofluoroalkenes.

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

Scanless two-photon voltage imaging.

Two-photon voltage imaging has long been heralded as a transformative approach capable of answering many long-standing questions in modern neuroscience. However, exploiting its full potential requires the development of novel imaging approaches well suited to the photophysical properties of genetically encoded voltage indicators. We demonstrate that parallel excitation approaches developed for scanless two-photon photostimulation enable high-SNR two-photon voltage imaging. We use whole-cell patch-clamp electrophysiology to perform a thorough characterization of scanless two-photon voltage imaging using three parallel illumination approaches and lasers with different repetition rates and wavelengths. We demonstrate voltage recordings of high-frequency spike trains and sub-threshold depolarizations from neurons expressing the soma-targeted genetically encoded voltage indicator JEDI-2P-Kv. Using a low repetition-rate laser, we perform multi-cell recordings from up to fifteen targets simultaneously. We co-express JEDI-2P-Kv and the channelrhodopsin ChroME-ST and capitalize on their overlapping two-photon absorption spectra to simultaneously evoke and image action potentials using a single laser source. We also demonstrate in vivo scanless two-photon imaging of multiple cells simultaneously up to 250 µm deep in the barrel cortex of head-fixed, anaesthetised mice.

Mitigating radiation-induced brain injury via NLRP3/NLRC4/Caspase-1 pyroptosis pathway: Efficacy of memantine and hydrogen-rich water.

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials.

PURPOSE: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials. DESIGN: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse. MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Detection and genomic characterization of Klebsiella pneumoniae and Escherichia coli harboring tet(X4) in black kites (Milvus migrans) in Pakistan.

The emergence of plasmid-mediated tigecycline resistance gene tet(X4) among clinically relevant bacteria has promoted significant concerns, as tigecycline is considered a last-resort drug against serious infections caused by multidrug-resistant bacteria. We herein focused on the isolation and molecular characterization of tet(X4)-positive Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) in wild bird populations with anthropogenic interaction in Faisalabad, Pakistan. A total of 150 birds including black kites (Milvus migrans) and house crows (Corvus splendens) were screened for the presence of tigecycline resistance K. pneumoniae and E. coli. We found two K. pneumoniae and one E. coli isolate carrying tet(X4) originating from black kites. A combination of short- and long-read sequencing strategies showed that tet(X4) was located on a broad host range IncFII plasmid family in K. pneumoniae isolates whereas on an IncFII-IncFIB hybrid plasmid in E. coli. We also found an integrative and conjugative element ICEKp2 in K. pneumoniae isolate KP8336. We demonstrate the first description of tet(X4) gene in the WHO critical-priority pathogen K. pneumoniae among wild birds. The convergence of tet(X4) and virulence associated ICEKp2 in a wild bird with known anthropogenic contact should be further investigated to evaluate the potential epidemiological implications. The potential risk of global transmission of tet(X4)-positive K. pneumoniae and E. coli warrant comprehensive evaluation and emphasizes the need for effective mitigation strategies to reduce anthropogenic-driven dissemination of AMR in the environment.

Breastfeeding Barriers for Preterm Infants in Neonatal Intensive Care Unit Environments: A Systematic Assessment and Meta-Analysis.

Background: Breast milk is vital for the growth and development of preterm infants. However, in Neonatal Intensive Care Units (NICUs), mothers often encounter significant challenges in breastfeeding. Objective: This study aims to systematically evaluate the barriers to breastfeeding in NICUs, thereby providing evidence-based support for clinical practices. Methods: A comprehensive search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, up to September 2023. Meta-analysis was performed using Stata 15.0, applying fixed or random effects models to calculate odds ratios (OR) and their 95% confidence intervals (CI). Study quality was assessed using the Newcastle-Ottawa Scale for cases and cohorts and the Agency for Healthcare Research and Quality standards for cross-sectional studies. Heterogeneity was evaluated using Cochran's chi-squared test (Cochran's Q) and I2 statistics, and publication bias was assessed through funnel plots and symmetry tests. Results: A total of 32 studies were included, encompassing 96,053 preterm infants. The main barriers to breastfeeding in preterm infants included: low gestational age (OR = 1.36, 95% CI: 1.06-1.75), lower maternal education (OR = 1.64, 95% CI: 1.39-1.93), insufficient breast milk (OR = 2.09, 95% CI: 1.39-1.93), multiple births (OR = 1.615, 95% CI: 1.18-2.210), smoking (OR = 2.906, 95% CI: 2.239-3.771), and single motherhood (OR = 1.439, 95% CI: 1.251-1.654). Conclusion: This study underscores the need for individualized breastfeeding support strategies in NICUs, taking into account the diverse backgrounds of mothers. Future research should focus on unraveling the underlying mechanisms affecting breastfeeding in preterm infants, with the goal of enhancing breastfeeding rates and improving developmental outcomes.

Enhanced osteogenesis and physicochemical properties of PMMA bone cement with SrBG/HA porous core-shell microspheres.

Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We preparedxSrBG@HA/PMMA cements (x= 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.

Photoinduced Decarboxylative Difluoroalkylation and Perfluoroalkylation of α-Fluoroacrylic Acids.

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

Development and validation of YARN: A novel SE-400 MPS kit for East Asian paternal lineage analysis.

Y-chromosomal short tandem repeat polymorphisms (Y-STRs) and Y-chromosomal single nucleotide polymorphisms (Y-SNPs) are valuable genetic markers used in paternal lineage identification and population genetics. Currently, there is a lack of an effective panel that integrates Y-STRs and Y-SNPs for studying paternal lineages, particularly in East Asian populations. Hence, we developed a novel Y-chromosomal targeted panel called YARN (Y-chromosome Ancestry and Region Network) based on multiplex PCR and a single-end 400 massive parallel sequencing (MPS) strategy, consisting of 44 patrilineage Y-STRs and 260 evolutionary Y-SNPs. A total of 386 reactions were validated for the effectiveness and applicability of YARN according to SWGDAM validation guidelines, including sensitivity (with a minimum input gDNA of 0.125 ng), mixture identification (ranging from 1:1-1:10), PCR inhibitor testing (using substances such as 50 µM hematin, 100 µM hemoglobin, 100 µM humic acid, and 2.5 mM indigo dye), species specificity (successfully distinguishing humans from other animals), repeatability study (achieved 100% accuracy), and concordance study (with 99.91% accuracy for 1121 Y-STR alleles). Furthermore, we conducted a pilot study using YARN in a cohort of 484 Han Chinese males from Huaiji County, Zhaoqing City, Guangdong, China (GDZQHJ cohort). In this cohort, we identified 52 different Y-haplogroups and 73 different surnames. We found weak to moderate correlations between the Y-haplogroups, Chinese surnames, and geographical locations of the GDZQHJ cohort (with λ values ranging from 0.050 to 0.340). However, when we combined two different categories into a new independent variable, we observed stronger correlations (with λ values ranging from 0.617 to 0.754). Overall, the YARN panel, which combines Y-STR and Y-SNP genetic markers, meets forensic DNA quality assurance guidelines and holds potential for East Asian geographical origin inference and paternal lineage analysis.

Forensic analysis and sequence variation of 133 STRs in the Hakka population.

Introduction: Short Tandem Repeats (STRs) are highly valuable genetic markers in forensic science. However, the conventional PCR-CE technique has limitations, and the emergence of massively parallel sequencing (MPS) technology presents new opportunities for STR analysis. Yet, there is limited research on Chinese population diversity using MPS. Methods: In this study, we obtained genotype data for 52 A-STRs and 81 Y-STRs from the Hakka population in Meizhou, Guangdong, China, using the Forensic Analysis System Multiplecues SetB Kit on the MGISEQ-2000 platform. Results: Our findings demonstrate that these 133 STRs are highly efficient for forensic applications within the Meizhou Hakka population. Statistical analysis revealed Hobs values ranging from 0.61306 to 0.91083 and Hexp values ranging from 0.59156 to 0.91497 for A-STRs based on length polymorphism. For sequence polymorphism, Hobs values ranged from 0.61306 to 0.94586, and Hexp values fluctuated between 0.59156 and 0.94487. The CPE values were 1-5.0779620E-21 and 1-3.257436E-24 for length and sequence polymorphism, respectively, while the CPD values were 1-1.727007E-59 and 1-5.517015E-66, respectively. Among the 80 Y-STR loci, the HD values for length and sequence polymorphism were 0.99764282 and 0.99894195, respectively. The HMP values stood at 0.00418102 and 0.00288427, respectively, and the DC values were 0.75502742 and 0.83363803, respectively. For the 52 A-STR loci, we identified 554 and 989 distinct alleles based on length and sequence polymorphisms, respectively. For the 81 Y-STR loci, 464 and 652 unique alleles were detected at the length and sequence level, respectively. Population genetic analysis revealed that the Meizhou Hakka population has a close kinship relationship with the Asian populations THI and KOR based on length polymorphism data of A-STRs. Conversely, based on length polymorphism data of Y-STRs, the Meizhou Hakka population has the closest kinship relationship with the Henan Han population. Discussion: Overall, the variation information of repeat region sequences significantly enhances the forensic identification efficacy of STR genetic markers, providing an essential database for forensic individual and paternity testing in this region. Additionally, the data generated by our study will serve as a vital resource for research into the genetic structure and historical origins of the Meizhou Hakka population.

Peripheral Blood Non-Coding RNA as Biomarker for Schizophrenia: A Review.

Schizophrenia (SCZ) is a complex and heterogeneous neuropsychiatric disorder that lacks objective diagnostic indicators and the pathogenesis remain unclear. Genetic factors may exert a significant impact on the development of the condition. While obtaining brain tissue for biopsy in the course of adjuvant diagnosis of SCZ patients may not be possible, the collection of peripheral blood is more accessible and easier to implement. In recent years, the development and application of RNA sequencing technology has made seeking biomarkers of SCZ becomes more feasible. There is emerging evidence suggesting that certain non-coding RNAs (ncRNA) are distinctly different in the peripheral blood of SCZ patients and healthy controls. Although the mechanisms remain unclear, these aberrantly expressed ncRNAs may be intimately associated with the onset and development of SCZ and may be of great significance for the diagnosis and treatment of SCZ. Therefore, we reviewed the expression of distinct types of ncRNAs that have been found in the peripheral blood of SCZ patients and explored their potential application as diagnostic biomarkers of SCZ. Differentially expressed ncRNAs in the peripheral blood of SCZ patients could not only serve as potential diagnostic biomarkers and therapeutic targets for SCZ but may also have implications for advancing understanding of the molecular mechanisms underlying the development of SCZ and elucidating the complex etiology of SCZ. Early diagnostic biomarkers obtained directly from peripheral blood are of great significance for the timely diagnosis and treatment of SCZ. Our review will enhance the comprehension of molecular mechanisms of SCZ and contribute to the identification of promising ncRNAs in peripheral blood for both diagnosis and therapy of SCZ.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Effect of breast milk intake volume on early behavioral neurodevelopment of extremely preterm infants.

BACKGROUND: This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks). METHODS: The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum. RESULTS: The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups. CONCLUSIONS: Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system.

Smartphone-based digital phenotyping for genome-wide association study of intramuscular fat traits in longissimus dorsi muscle of pigs.

Intramuscular fat (IMF) content and distribution significantly contribute to the eating quality of pork. However, the current methods used for measuring these traits are complex, time-consuming and costly. To simplify the measurement process, this study developed a smartphone application (App) called Pork IMF. This App serves as a rapid and portable phenotyping tool for acquiring pork images and extracting the image-based IMF traits through embedded deep-learning algorithms. Utilizing this App, we collected the IMF traits of the longissimus dorsi muscle in a crossbred population of Large White × Tongcheng pigs. Genome-wide association studies detected 13 and 16 SNPs that were significantly associated with IMF content and distribution, respectively, highlighting NR2F2, MCTP2, MTLN, ST3GAL5, NDUFAB1 and PID1 as candidate genes. Our research introduces a user-friendly digital phenotyping technology for quantifying IMF traits and suggests candidate genes and SNPs for genetic improvement of IMF traits in pigs.