In Situ Biosynthesis of FeS Nanoparticles Boosts Current Generation in Bioelectrochemical Systems Through Efficient Electron Transfer.

The utility of electrochemical active biofilm in bioelectrochemical systems has received considerable attention for harvesting energy and chemical products. However, the slow electron transfer between biofilms and electrodes hinders the enhancement of performance and still remains challenging. Here, using Fe3O4 /L-Cys nanoparticles as precursors to induce biomineralization, a facile strategy for the construction of an effective electron transfer pathway through biofilm and biological/inorganic interface is proposed, and the underlying mechanisms are elucidated. Taking advantage of an on-chip interdigitated microelectrode array (IDA), the conductive current of biofilm that is related to the electron transfer process within biofilm is characterized, and a 2.10-fold increase in current output is detected. The modification of Fe3O4/L-Cys on the electrode surface facilitates the electron transfer between the biofilm and the electrode, as the bio/inorganic interface electron transfer resistance is only 16% compared to the control. The in-situ biosynthetic Fe-containing nanoparticles (e.g., FeS) enhance the transmembrane EET and the EET within biofilm, and the peak conductivity increases 3.4-fold compared to the control. The in-situ biosynthesis method upregulates the genes involved in energy metabolism and electron transfer from the transcriptome analysis. This study enriches the insights of biosynthetic nanoparticles on electron transfer process, holding promise in bioenergy conversion.

Lysosome-Targeted and pH-Activatable Phototheranostics for NIR-II Fluorescence Imaging-Guided Nasopharyngeal Carcinoma Phototherapy.

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC. A lysosome-targeted S-D-A-D-S-type NIR-II phototheranostic molecule (IRFEM) is encapsulated within the acid-sensitive amphiphilic DSPE-Hyd-PEG2k to form IRFEM@DHP nanoparticles (NPs). The prepared IRFEM@DHP exhibits a good accumulation in the acidic lysosomes for facilitating the release of IRFEM, which could disrupt lysosomal function by generating an amount of heat and ROS under laser irradiation. Moreover, the guidelines of NIR-II fluorescence enhance the accuracy of PTT/PDT for NPC and avoid damage to normal tissues. Remarkably, IRFEM@DHP enable efficient antitumor effects both in vitro and in vivo, opening up a new avenue for precise NPC theranostics.

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway.

Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11ß-Hydroxysteroid dehydrogenase-2 (11ß-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11ß-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down-regulation of 11ß-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis-induced placental dysfunction and subsequent FGR.

Controllable Pyridine N-Oxidation-Nucleophilic Dechlorination Process for Enhanced Dechlorination of Chloropyridines: The Cooperation of HCO4- and HO2.

Dechlorination of chloropyridines can eliminate their detrimental environmental effects. However, traditional dechlorination technology cannot efficiently break the C-Cl bond of chloropyridines, which is restricted by the uncontrollable nonselective species. Hence, we propose the carbonate species-activated hydrogen peroxide (carbonate species/H2O2) process wherein the selective oxidant (peroxymonocarbonate ion, HCO4-) and selective reductant (hydroperoxide anion, HO2-) controllably coexist by manipulation of reaction pH. Taking 2-chloropyridine (Cl-Py) as an example, HCO4- first induces Cl-Py into pyridine N-oxidation intermediates, which then suffer from the nucleophilic dechlorination by HO2-. The obtained dechlorination efficiencies in the carbonate species/H2O2 process (32.5-84.5%) based on the cooperation of HCO4- and HO2- are significantly higher than those in the HO2--mediated sodium hydroxide/hydrogen peroxide process (0-43.8%). Theoretical calculations confirm that pyridine N-oxidation of Cl-Py can effectively lower the energy barrier of the dechlorination process. Moreover, the carbonate species/H2O2 process exhibits superior anti-interference performance and low electric energy consumption. Furthermore, Cl-Py is completely detoxified via the carbonate species/H2O2 process. More importantly, the carbonate species/H2O2 process is applicable for efficient dehalogenation of halogenated pyridines and pyrazines. This work offers a simple and useful strategy to enhance the dehalogenation efficiency of halogenated organics and sheds new insights into the application of the carbonate species/H2O2 process in practical environmental remediation.

Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients.

OBJECTIVES: To describe the pharmacokinetic (PK) characteristics of nirmatrelvir/ritonavir in renal transplant recipients and explore the potential factors that related to the PK variance of nirmatrelvir/ritonavir and its interaction with calcineurin inhibitor (CNI). METHODS: Renal transplant recipients treated with CNI and nirmatrelvir/ritonavir were prospectively enrolled. Steady-state plasma concentrations of nirmatrelvir/ritonavir were determined by high-performance liquid chromatography-tandem mass spectrometry, and the PK parameters were calculated using non-compartmental analysis. Spearman correlation analysis was used for exploring influencing factors. RESULTS: A total of eight recipients were enrolled; for nirmatrelvir and ritonavir, AUC/dose was 0.24179 ± 0.14495 and 0.06196 ± 0.03767 µg·h·mL-1·mg-1. Red blood cell (RBC), hematocrit (Ht), hemoglobins (Hb), and creatinine clearance (Ccr) were negatively correlated with AUC/dose of nirmatrelvir, while Ccr, CYP3A5 genotype, and CYP3A4 genotype were related to the AUC/dose of ritonavir. Ccr was negatively correlated with the C0/dose of tacrolimus (TAC) after termination of nirmatrelvir/ritonavir (rs = -0.943, p = 0.008). CONCLUSIONS: The PK characteristics of nirmatrelvir/ritonavir vary greatly among renal transplant recipients. Factors including Ccr and CYP3A5 genotype were related to the in vivo exposure of nirmatrelvir/ritonavir. During the whole process before and after nirmatrelvir/ritonavir therapy, it is recommended to adjust the CNI basing on renal function to avoid CNI toxicity exposure.

Behavioral and molecular response of the insect parasitic nematode Steinernema carpocapsae to plant volatiles.

Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.

Value of original and modified pathological scoring systems for prognostic prediction in paraffin-embedded donor kidney core biopsy.

BACKGROUND: No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy. METHODS: A total of 185 donor kidney CB specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores. RESULTS: The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59, p < 0.001; PGF: OR = 1.06, p = 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems. CONCLUSIONS: Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section.

How Integrated Digital Tools Can Improve Tuberculosis Medication Adherence: A Longitudinal Study in China.

Background: Poor medication adherence remains one of the major problems in the treatment of tuberculosis (TB) patients, while digital technologies have been proven effective to improve the treatment results. However, reports on the effectiveness of comprehensive practice integrating different intervention methods and technologies are limited. The aim of this study is to evaluate the effectiveness of an integrated digital adherence intervention for TB patients. Methods: We developed a digital adherence intervention platform integrating instant WeChat message, electronic medication monitors (EMMs), and manual reminders. The primary goal of the platform was to improve the accessibility of digital adherence technologies, and thus improve treatment adherence. TB patients were newly diagnosed at 10 TB-designated hospitals and came from 220 communities, from January to June 2022. The basic characteristics and treatment adherence of TB patients in WeChat, EMM, and conventional groups were compared, and the influencing factors of high medication adherence were analyzed by logistic regression. Results: A total of 2,498 TB patients were enrolled in the study, 14.5% were managed by digital technologies, 9.5% by WeChat, and 5.0% by EMM, respectively. After intervention, the median medication rate of TB patients was significantly higher in the WeChat group (95.3%) and EMM group (95.7%) compared with that of the conventional group (83.8%). On the contrary, the median number of missed medications among patients of the conventional group (nine times) was significantly higher than that in the WeChat (three times) group and EMM (three times) group. The proportion of high adherence (adherence medication rate ≥90%) among TB patients was 64.7%, 64.5%, and 43.2% in WeChat, EMM, and conventional group, respectively. Conclusions: The application of the integrated digital adherence intervention platform could significantly improve medication adherence among TB patients. The accessibility of digital adherence technologies could be improved by integrating complementary technologies in practice.

Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

[Analysis and reflection on current situation of Chinese patent medicine for children in China].

This study took Chinese patent medicine for children included in Chinese Pharmacopoeia(2020 edition and the first supplement), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2022 edition), and National Essential Medicines List(2018 edition) as the research objects, so as to sort out the distribution situation, characteristics, and the problems of Chinese patent medicine for children(including child-specific medicines, common medicines for children and adults, and discretionary medicines for children). According to statistics and summary, Chinese patent medicine for children is mainly administered orally, and the dosage forms are mostly traditional dosage forms, such as tablets, granules, capsules, and oral liquids, with mostly bitter or sweet taste. Diseases are mainly classified into pulmonary diseases and spleen and stomach diseases, and varieties of medication without Children's medication safety information or "still unclear" account for a relatively large proportion of the medicines. There are relatively few varieties of Chinese patent medicines for children, poor compliance of child-specific medication, lack of refinement of Chinese patent medicines for children dosage, and lack of information about safe use of medication. It is recommended to update and improve the instruction manuals in a timely manner, develop new varieties of Chinese patent medicine for children, and actively carry out post-marketing evaluation and clinical comprehensive evaluation of Chinese patent medicine for children, so as to provide a reference for the supplement and improvement of the instructions, the comprehensive improvement, the formulation of the catalogue, and the research and development of new Chinese patent medicine for children and ensure the use of medicines for children.

Tumor Microenvironment-Responsive One-for-All Molecular-Engineered Nanoplatform Enables NIR-II Fluorescence Imaging-Guided Combinational Cancer Therapy.

The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.

Ni Single Atoms Embedded in Graphene Nanoribbon Sieves for High-Performance CO2 Reduction to CO.

Ni single-atom catalysts (SACs) are appealing for electrochemical reduction CO2 reduction (CO2 RR). However, regulating the balance between the activity and conductivity remains a challenge to Ni SACs due to the limitation of substrates structure. Herein, the intrinsic performance enhancement of Ni SACs anchored on quasi-one-dimensional graphene nanoribbons (GNRs) synthesized is demonstrated by longitudinal unzipping carbon nanotubes (CNTs). The abundant functional groups on GNRs can absorb Ni atoms to form rich Ni-N4 -C sites during the anchoring process, providing a high intrinsic activity. In addition, the GNRs, which maintain a quasi-one-dimensional structure and possess a high conductivity, interconnect with each other and form a conductive porous framework. The catalyst yields a 44 mA cm-2 CO partial current density and 96% faradaic efficiency of CO (FECO ) at -1.1 V vs RHE in an H-cell. By adopting a membrane electrode assembly (MEA) flow cell, a 95% FECO and 2.4 V cell voltage are achieved at 200 mA cm-2 current density. This work provides a rational way to synthesize Ni SACs with a high Ni atom loading, porous morphology, and high conductivity with potential industrial applications.

Microstructure Design Strategy for Molecularly Dispersed Cobalt Phthalocyanine and Efficient Mass Transport in CO2 Electroreduction.

Cobalt phthalocyanine (CoPc) has attracted particular interest owing to its excellent activity during the electrochemical CO2 conversion to CO. However, the efficient utilization of CoPc at industrially relevant current densities is still a challenge owing to its nonconductive property, agglomeration, and unfavorable conductive substrate design. Here, a microstructure design strategy for dispersing CoPc molecules on a carbon substrate for efficient CO2 transport during CO2 electrolysis is proposed and demonstrated. The highly dispersed CoPc is loaded on a macroporous hollow nanocarbon sheet to act as the catalyst (CoPc/CS). The unique interconnected and macroporous structure of the carbon sheet forms a large specific surface area to anchor CoPc with high dispersion and simultaneously boosts the mass transport of reactants in the catalyst layer, significantly improving the electrochemical performance. By employing a zero-gap flow cell, the designed catalyst can mediate CO2 to CO with a high full-cell energy efficiency of 57% at 200 mA cm-2 .

Boosting Carbon Dioxide Reduction in a Photocatalytic Fuel Cell with a Bubbling Fluidized Cathode: Dual Function of Titanium Carbide.

Photoelectrochemical reduction of carbon dioxide (CO2) is a promising avenue to realize resourceful utilization of carbon dioxide and mitigate the energy shortage. Herein, a photocatalytic fuel cell with a bubbling fluidized cathode (PFC-BFC) is proposed to increase the performance of the photocatalytic CO2 reduction reaction (CO2RR). Titanium carbide (Ti3C2) is first used as a fluidized cathode catalyst with the dual features of superior capacitance and high CO2RR catalytic activity. Compared with the conventional PFC system, the as-proposed PFC-BFC system exhibits a higher gas production performance. Particularly, the generation rate and Faraday efficiency for CH4 production reach to 37.2 µmol g-1 h-1 and 72%, which are 10.9 and 6.5 times higher than that of the conventional PFC system, respectively. The bubbling fluidized cathode allows a rapid electron transfer between catalysts and the current collector and an efficient diffusion of catalysts in the whole solution, thus remarkably increasing the effective reaction area of the CO2RR. In addition, the fluidized reaction mechanism of charging/discharging-coupled CO2RR is investigated. Significantly, a magnified PFC-BFC system is designed and exhibits a similar gas generation rate compared to that of the small-scale system, indicating a good potential of scaling up in the industry applications. These results demonstrated that the proposed PFC-BFC system can maximize the utilization of catalyst active sites and enhance the reaction kinetics, providing an alternative design for the application of CO2RR.

Characteristics of children with IgA nephropathy.

BACKGROUND: We analyzed the demographic and clinical characteristics of children with immunoglobulin A (IgA) nephropathy using data in the first pages of electronic health records of 22 hospitals from 2016 to 2018. METHODS: Information collected included gender, age, infection site, etiological infection, acute kidney injury (AKI), and chronic kidney disease (CKD) stages 2-5. We analyzed the gender and age distribution of children with IgA nephropathy, the characteristics of children complicated with AKI and CKD, and the influence of geographical distribution and economic status on the incidence of IgA nephropathy. RESULTS: We included a total of 4006 patients with IgA nephropathy. Incidence in males gradually increased with age. Seventy-nine cases (1.97%) had AKI. We found no significant difference in gender (P = 0.19) or age (P = 0.07) between the AKI and non-AKI groups. Twenty-nine patients had CKD (0.72%), who were significantly older than those in the non-CKD group (P < 0.0001). The incidence of IgA nephropathy in less-developed areas was significantly lower than that in developed areas (P = 0.0002). CONCLUSIONS: The incidence of IgA nephropathy was high mainly in males. Age was an important factor affecting CKD. The disease was related to environment and economic status. IMPACT: We analyze the demographic and clinical characteristics of children with immunoglobulin A (IgA) nephropathy using data in the first pages of electronic health records. This is a large sample, multi-center study. The incidence of IgA nephropathy in males increased gradually with age. Age was an important factor affecting CKD. The disease was related to environment and economic status.

In Situ Probing the Mass Transport Property Inside an Imitated Three-Dimensional Porous Bioelectrode.

Three-dimensional porous materials have been demonstrated as the most successful bioelectrodes in bioelectrochemical systems due to their high specific surface area and abundant adhesion regions for electroactive bacteria. However, the pore clogging potentially limits the mass transfer process inside the electrode due to the unreasonable structure design and long-term operation. The investigation of mass transport behavior in the porous scaffolds is of great significance for designing the electrode structure and optimizing bioelectrochemical system performance. To in situ characterize the mass transport behavior in the orderly pore structure, model electrodes with 100 copper wires (10 × 10) are constructed to imitate a three-dimensional porous structure (pore size: ∼150 µm) commonly employed in bioelectrodes. The poor proton effective diffusion coefficient solidly demonstrates that the mass transport inside the three-dimensional porous electrode is critically inhibited, leading not only to a progressive change and sparse biomass in the biofilm development process but also to biofilm acidification due to serious proton accumulation. It finally results in sluggish bacterial metabolic activity and a decreased electrocatalytic capacity. The interior space of porous electrodes cannot be adequately utilized, resulting in the inability to fully exploit the advantages of their abundant surface area. Consequently, the construction of gradient porous electrodes with small inner and large outer pores to enhance mass transport is a feasible proposal for enhancing performance. The proposed methodology of establishing model electrodes combined with the in situ detection technique within porous electrodes is crucial for acquiring various types of physicochemical information inside the bioelectrode, such as biofilm growth situation, biochemical reaction conditions, as well as mass transfer characteristics. More importantly, the work provides a fundamental basis for designing highly efficient bioelectrodes.

Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transplantation strategies of different phenotypes. METHODS: The records of children with NPHP treated at our center from 01/2018 to 03/2021 were retrospectively reviewed. Inclusion criteria were a diagnosis of NPHP, received kidney transplantation, and received whole exome sequencing (WES) or nephropathy gene panel testing. RESULTS: Twenty-nine children with NPHP were included. Nine children (31%) had NPHP1 mutations, and all presented with isolated nephropathy. Eighteen of 20 patients with non-NPHP1 mutations had compound heterozygous mutations, and 70% had extrarenal phenotype. Age at disease presentation (11.2 ± 1.94 years) and the development of kidney failure (12.4 ± 2.70 years) were later in children with NPHP1 mutations than those with non-NPHP1 mutations (5.2 ± 2.83 years and 5.7 ± 2.92 years, respectively). Four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis. Isolated kidney transplantation resulted in good outcomes for patients with mild or moderate liver fibrosis without portal hypertension, while cholestasis was common postoperatively and could be resolved with ursodeoxycholic acid. CONCLUSIONS: NPHP1 mutations are the most common in children with NPHP, and the phenotype of NPHP1 mutation is significantly different from that of non-NPHP1 mutation. For NPHP patients with mild to moderate liver fibrosis without portal hypertension, timely treatment of cholestasis could prevent the rapid progression of liver function damage after isolated kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cochlear Implant Facilitates the Use of Talker Sex and Spatial Cues to Segregate Competing Speech in Unilaterally Deaf Listeners.

OBJECTIVES: Talker sex and spatial cues can facilitate segregation of competing speech. However, the spectrotemporal degradation associated with cochlear implants (CIs) can limit the benefit of talker sex and spatial cues. Acoustic hearing in the nonimplanted ear can improve access to talker sex cues in CI users. However, it's unclear whether the CI can improve segregation of competing speech when maskers are symmetrically placed around the target (i.e., when spatial cues are available), compared with acoustic hearing alone. The aim of this study was to investigate whether a CI can improve segregation of competing speech by individuals with unilateral hearing loss. DESIGN: Speech recognition thresholds (SRTs) for competing speech were measured in 16 normal-hearing (NH) adults and 16 unilaterally deaf CI users. All participants were native speakers of Mandarin Chinese. CI users were divided into two groups according to thresholds in the nonimplanted ear: (1) single-sided deaf (SSD); pure-tone thresholds <25 dB HL at all audiometric frequencies, and (2) Asymmetric hearing loss (AHL; one or more thresholds > 25 dB HL). SRTs were measured for target sentences produced by a male talker in the presence of two masker talkers (different male or female talkers). The target sentence was always presented via loudspeaker directly in front of the listener (0°), and the maskers were either colocated with the target (0°) or spatially separated from the target at ±90°. Three segregation cue conditions were tested to measure masking release (MR) relative to the baseline condition: (1) Talker sex, (2) Spatial, and (3) Talker sex + Spatial. For CI users, SRTs were measured with the CI on or off. RESULTS: Binaural MR was significantly better for the NH group than for the AHL or SSD groups ( P < 0.001 in all cases). For the NH group, mean MR was largest with the Talker sex + spatial cues (18.8 dB) and smallest for the Talker sex cues (10.7 dB). In contrast, mean MR for the SSD group was largest with the Talker sex + spatial cues (14.7 dB), and smallest with the Spatial cues (4.8 dB). For the AHL group, mean MR was largest with the Talker sex + spatial cues (7.8 dB) and smallest with the Talker sex (4.8 dB) and the Spatial cues (4.8 dB). MR was significantly better with the CI on than off for both the AHL ( P = 0.014) and SSD groups ( P < 0.001). Across all unilaterally deaf CI users, monaural (acoustic ear alone) and binaural MR were significantly correlated with unaided pure-tone average thresholds in the nonimplanted ear for the Talker sex and Talker sex + spatial conditions ( P < 0.001 in both cases) but not for the Spatial condition. CONCLUSION: Although the CI benefitted unilaterally deaf listeners' segregation of competing speech, MR was much poorer than that observed in NH listeners. Different from previous findings with steady noise maskers, the CI benefit for segregation of competing speech from a different talker sex was greater in the SSD group than in the AHL group.

Dysfunction of VIPR2 leads to myopia in humans and mice.

BACKGROUND: Myopia is the leading cause of refractive errors. As its pathogenesis is poorly understood, we determined if the retinal VIP-VIPR2 signalling pathway axis has a role in controlling signalling output that affects myopia development in mice. METHODS: Association analysis meta-study, single-cell transcriptome, bulk RNA sequencing, pharmacological manipulation and VIPR2 gene knockout studies were used to clarify if changes in the VIP-VIPR2 signalling pathway affect refractive development in mice. RESULTS: The SNP rs6979985 of the VIPR2 gene was associated with high myopia in a Chinese Han cohort (randomceffect model: p=0.013). After either 1 or 2 days' form deprivation (FD) retinal VIP mRNA expression was downregulated. Retinal single-cell transcriptome sequencing showed that VIPR2 was expressed mainly by bipolar cells. Furthermore, the cAMP signalling pathway axis was inhibited in some VIPR2+ clusters after 2 days of FD. The selective VIPR2 antagonist PG99-465 induced relative myopia, whereas the selective VIPR2 agonist Ro25-1553 inhibited this response. In Vipr2 knockout (Vipr2-KO) mice, refraction was significantly shifted towards myopia (p<0.05). The amplitudes of the bipolar cell derived b-waves in 7-week-old Vipr2-KO mice were significantly larger than those in their WT littermates (p<0.05). CONCLUSIONS: Loss of VIPR2 function likely compromises bipolar cell function based on presumed changes in signal transduction due to altered signature electrical wave activity output in these mice. As these effects correspond with increases in form deprivation myopia (FDM), the VIP-VIPR2 signalling pathway axis is a viable novel target to control the development of this condition.

Trends of a decade in risk factors of patient delay among pulmonary tuberculosis patients during fast aging and urbanization - analysis of surveillance data from 2008 to 2017 in Wuhan, China.

BACKGROUND: Tuberculosis (TB) is a leading infectious cause of morbidity and mortality worldwide. However, delay in health care seeking has remained unacceptably high. The aim of this study was to clarify the trend of patient delay and its associated risk factors during rapid aging and urbanization in Wuhan, China from 2008 to 2017. METHODS: A total of 63,720 TB patients registered at Wuhan TB Information Management System from January 2008 to December 2017 were included. Long patient delay (LPD) was defined as patient delay longer than 14 days. Independent associations of area and household identity with LPD, as well their interaction effect, were tested by logistic regression models. RESULTS: Among 63,720 pulmonary TB patients, 71.3% were males, the mean age was 45.5 ± 18.8 years. The median patient delay was 10 days (IQR, 3-28). A total of 26,360 (41.3%) patients delayed for more than 14 days. The proportion of LPD decreased from 44.8% in 2008 to 38.3% in 2017. Similar trends were observed in all the subgroups by gender, age and household, except for living area. The proportion of LPD decreased from 46.3 to 32.8% in patients living near downtown and increased from 43.2 to 45.2% in patients living far from downtown. Further interaction effect analysis showed that among patients living far from downtown, the risk of LPD for local patients increased with age, while decreased with age for migrant patients. CONCLUSION: Although the overall LPD among pulmonary TB patients declined in the past decade, the extent of reduction varied in different subgroups. The elderly local and young migrant patients living far from downtown are the most vulnerable groups to LPD in Wuhan, China.