Search

Abstract Background Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. Methods In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. Results The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. Conclusions The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.

In the early Qing dynasty, there was a Southern Song dynasty woodblock-printed edition of Du Gong Bu ji (杜工部集), which was composed of reprinted editions of Er Wang Ben (二王本) and Wu Ruo Ben (吳若本). Later, the book became incomplete. Four handwritten copies of the book have survived to this day. Among them, Mao Jin Ben (毛晉本) in Seikado Bunko of Japan (日本靜嘉堂文庫), which is the ancestor of the extant handwritten copies, is the closest to the Song dynasty edition. Mao Yi pointed out that Mao Jin Ben was an apograph. But the Mao Jin Ben is just an ordinary manuscript. Shanghai Library of Mao Yi Ben (毛扆本) was added based on remaining part of original books of the Song dynasty. The supplementary content is based on Mao Jin Ben. In the process of copying, Mao Yi collated Mao Jin Ben based on Qian Zhu Du Shi (錢注杜詩), which led to the loss of Mao Yi Ben and even the original appearance of the Song dynasty edition. The Qian Zeng Ben (錢曾本) of the National Library of China and the handwritten copies of the National Library of Taiwan were instead part of the Mao Jin transcription system. Compared with the Mao Jin Ben, the extra part of Qian Zeng Ben comes from “Qian Zhu Du Shi.” (Article content in Chinese with English extended abstract)

This work investigated the microstructure and impact behavior of Mg-4Al-5RE-xGd (RE represents La-Ce mischmetal; x = 0, 0.2, 0.7 wt.%) alloys cast by high-pressure die casting (HPDC), permanent mold casting (PMC), and sand casting (SC) techniques. The results indicated that with increasing Gd content, the grain sizes of the HPDC alloy had a slight change, but the grains of the PMC and SC alloys were significantly refined. Besides, the acicular Al11RE3 phase was modified into the short-rod shape under the three casting conditions. The impact toughness of the studied alloy was mainly dominated by the absorbed energy during the crack initiation. With increasing Gd content, the impact toughness of the studied alloy monotonically increased due to the lower tendency of the modified second phase toward crack initiation. The impact stress was higher than the tensile stress, exhibiting a strain rate sensitivity for the mechanical response; however, the HPDC alloy had an inconsistent strain rate sensitivity during the impact event due to the transformation of the deformation mechanism from twinning to slip with increasing strain. Abundant dimples covered the fracture surface of the fine-grained HPDC alloys, indicating a typical ductile fracture. Nevertheless, due to the deficient {101¯2} twinning activity and the suppressed grain boundary sliding during the impact event, the HPDC alloys showed insufficient plastic deformation capacity.

Abstract The nitrate (NO3 −) electroreduction into ammonia (NH3) represents a promising approach for sustainable NH3 synthesis. However, the variation of adsorption configurations renders great difficulties in the simultaneous optimization of binding energy for the intermediates. Though the extensively reported Cu-based electrocatalysts benefit NO3 − adsorption, one of the key issues lies in the accumulation of nitrite (NO2 −) due to its weak adsorption, resulting in the rapid deactivation of catalysts and sluggish kinetics of subsequent hydrogenation steps. Here we report a tandem electrocatalyst by combining Cu single atoms catalysts with adjacent Co3O4 nanosheets to boost the electroreduction of NO3 − to NH3. The obtained tandem catalyst exhibits a yield rate for NH3 of 114.0 mg $${}_{{{{{{\rm{NH}}}}}}_3}$$ NH 3 h−1 cm−2, which exceeds the previous values for the reported Cu-based catalysts. Mechanism investigations unveil that the combination of Co3O4 regulates the adsorption configuration of NO2 − and strengthens the binding with NO2 −, thus accelerating the electroreduction of NO3 − to NH3.

Abstract The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

Abstract Background Splicing factor B subunit 4 (SF3B4) has been confirmed to participate in the progression of many cancers and is considered to be a potential target for non‐small cell lung cancer (NSCLC). Thus, the role and molecular mechanism of SF3B4 in NSCLC progression deserves further study. Methods Quantitative real‐time PCR and western blot were employed to detect the mRNA and protein levels of SF3B4, Sm‐like protein 4 (LSM4) and methyltransferase‐like 3 (METTL3). Cell proliferation, apoptosis, invasion, migration and stemness were tested by cell counting kit‐8, colony formation, flow cytometry, transwell, wound healing, and sphere formation assays. The interaction between SF3B4 and METTL3 or LSM4 was confirmed by MeRIP, RIP and Co‐IP assays. Mice xenograft models were constructed to assess the effects of METTL3 and SF3B4 on NSCLC tumorigenesis. Results SF3B4 had high expression in NSCLC tissues and was associated with the shorter overall survival of NSCLC patients. Knockdown of SF3B4 suppressed NSCLC cell proliferation, invasion, migration and stemness, while inducing apoptosis. METTL3 promoted SF3B4 mRNA stability by m6A modification, and its knockdown inhibited NSCLC cell growth, metastasis and stemness by downregulating SF3B4. SF3B4 could interact with LSM4, and sh‐SF3B4‐mediated the inhibition on NSCLC cell functions could be reversed by LSM4 overexpression. In addition, reduced METTL3 expression restrained NSCLC tumor growth, and this effect was reversed by SF3B4 overexpression. Conclusion METTL3‐stablized SF3B4 promoted NSCLC cell growth, metastasis and stemness via positively regulating LSM4.

Abstract Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Abstract Objectives Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample. Methods Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities. Results In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS. Conclusion In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.

Abstract RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Lower urinary tract symptoms (LUTS) are defined as symptoms related to the lower urinary tract or referred from similarly innervated anatomy. No specific criteria are used to precisely define LUTS owing to its multiorgan involvement instead of organ-centric (urethra and bladder). In the past decade, the prevalence of LUTS dramatically increased owing to low health care seeking behaviors. Initially, patients with LUTS seemed to not actively look for medical opinions because of cultural or ethnic barriers. Raising awareness of the significance of medical opinions may contribute to increasing health care seeking behaviors for LUTS. In addition to the association between LUTS and mental illness, a temporal relationship exists, that is, LUTS may cause mental illness and vice versa. This bidirectional correlation relationship was demonstrated by a nationwide observational study. The impacts of LUTS vary among different age groups. Older adults have higher LUTS prevalence, whereas younger ones with LUTS have higher risks of developing anxiety and depression. Similarly, the impacts of LUTS differ between men and women. Women have higher LUTS prevalence; however, men with LUTS have higher risks of developing anxiety and depression. In conclusion, significant association and temporal bidirectional relationship exist between LUTS and mental health. Our findings suggested that patients with LUTS also receive mental illness–related health care; similarly, patients with mental illness may have risks of developing subsequent LUTS.

Abstract The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibition is recognized for its evident renoprotective benefits in diabetic renal disease. Recent data suggest that SGLT2 inhibition also slows down kidney disease progression and reduces the risk of acute kidney injury, regardless of whether the patient has diabetes or not, but the mechanism behind these observed effects remains elusive. The objective of this study is to utilize a mendelian randomization (MR) methodology to comprehensively examine the influence of metabolites in circulation regarding the impact of SGLT2 inhibition on kidney function. Methods We used a MR study to obtain associations between genetic proxies for SGLT2 inhibition and kidney function. We retrieved the most recent and comprehensive summary statistics from genome-wide association studies (GWAS) that have been previously published and involved kidney function parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria. Additionally, we included blood metabolite data from 249 biomarkers in the UK Biobank for a more comprehensive analysis. We performed MR analyses to explore the causal relationships between SGLT2 inhibition and kidney function and two-step MR to discover potential mediating metabolites. Results The study found that a decrease in HbA1c levels by one standard deviation, which is genetically expected to result in SGLT2 inhibition, was linked to a decreased likelihood of developing type 2 diabetes mellitus (T2DM) (odds ratio [OR] = 0.55 [95% CI 0.35, 0.85], P = 0.007). Meanwhile, SGLT2 inhibition also protects eGFR (β = 0.05 [95% CI 0.03, 0.08], P = 2.45 × 10− 5) and decreased UACR (-0.18 [95% CI -0.33, -0.02], P = 0.025) and albuminuria (-1.07 [95% CI -1.58, -0.57], P = 3.60 × 10− 5). Furthermore, the study found that of the 249 metabolites present in the blood, only one metabolite, specifically the concentration of small high-density lipoprotein (HDL) particles, was significantly correlated with both SGLT2 inhibition and kidney function. This metabolite was found to play a crucial role in mediating the improvement of renal function through the use of SGLT2 inhibition (β = 0.01 [95% CI 0.005, 0.018], P = 0.001), with a mediated proportion of 13.33% (95% CI [5.71%, 26.67%], P = 0.020). Conclusions The findings of this investigation provide evidence in favor of a genetically anticipated biological linkage between the inhibition of SGLT2, the presence of circulating metabolites, and renal function. The findings demonstrate that the protective effect of SGLT2 inhibition on renal function is mostly mediated by HDL particle concentrations in circulating metabolites. These results offer significant theoretical support for both the preservation of renal function and a better comprehension of the mechanisms underlying SGLT2 inhibition.

Abstract Background Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes. Methods Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes. Results In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among “Mild P-A” at baseline, 32.0% converted to no-pain, 12.8% progressed to “Mild P-R-A”, and 53.2% remained. Approximately 46.1% of “Mild P-R-A” and 54.5% of “Mod P-R-A” at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade. Conclusions We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.

Wasp venom injections from wasp stings can damage several organs, most commonly the kidneys. Despite literature evidence, wasp sting-induced acute kidney injury (AKI) is rare and involves complex pathophysiological processes. While acute tubular necrosis (ATN) is the most prevalent histological result of wasp sting-induced AKI, uncommon combinations of chronic renal lesions have been described, alerting us to the patient's underlying illness. We report a 55-year-old hypertensive patient with unknown renal function who got AKI following multiple wasp stings. His renal function had not improved after continuous hemodialysis and plasma exchange; therefore, a kidney biopsy was performed. The pathology revealed that in addition to ATN, his kidney's distinguishing feature was a mix of chronic interstitial renal disease and chronic glomerulosclerosis. We think that his current renal pathological results were caused by hypertension in addition to wasp venom.

Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1β, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflammation, and apoptosis in the traumatic brain injury model. Treatment with DMF effectively reversed these changes, alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway, ultimately conferring protection against AKI. Activating Keap1-Nrf2/HO-1 signaling pathway may be a potential therapeutic strategy for attenuating oxidative stress-induced AKI after TBI.

IntroductionIn the aftermath of the COVID-19 pandemic, the reintegration of Chinese international student returnees intersects with China’s critical effort to combat a significant brain drain of highly skilled talents, highlighting an unprecedented psychological battleground. This convergence underscores the urgent need for nuanced research to navigate the uncharted territory of their mental health.MethodsEmploying Bayesian analysis supported by Markov Chain Monte Carlo (MCMC) algorithms, this study examined depression prevalence and associated factors among 1,014 Chinese returnees. The sample comprised 44.87% male participants (455), 51.58% female participants (523), and 3.55% identifying as “Others” (36), with an age distribution of 61.74% aged 18-30 (626), 28.80% aged 31-40 (292), and 9.47% aged 41-50 (96). The mean age of participants was 29.6 years, ranging from 18 to 50 years. PHQ-9 diagnoses revealed alarming levels of depression, with 47.9% exhibiting a moderately severe degree of depressive disorder.ResultsOur findings highlight the intricate interplay between identity clusters— “homestayers” (those leaning towards a Chinese cultural identity), “navigators” (those with a bicultural identity), and “wayfarers” (those leaning towards a foreign cultural identity)—and the likelihood of depression. Specifically, homestayers showed a clear and strong negative association, navigators demonstrated a positive association, and wayfarers had a positive yet unclear correlation with depression levels. Furthermore, acculturation, age, and gender showed no significant effects, whereas education mildly mitigated depression.DiscussionBased on these findings, we suggest the implementation of better-tailored mental health support and policies to facilitate smoother reintegration.

A novel AlGaN/GaN HEMT is proposed to improve its single event transient (SET) effect and breakdown characteristics. The device features an AlGaN back barrier layer and a buried P-GaN island in the back barrier layer (BP-HEMT). First, the P-GaN island not only modulates the electric field distribution and reduces impact ionization at both the blocking state and after ion strike but also increases the hole-electron recombination rate. Therefore, it not only effectively increases the breakdown voltage (BV), but also improves the anti-SET performance owing to decreasing the current peak after ion strike. Second, the AlGaN back barrier confines electrons in the channel, and thus, on one hand, it is beneficial to the high saturation drain current (Id,sat) and low on-state resistance (Ron); on the other hand, it effectively prevents the electrons in the buffer layer introduced by ion strike from reaching the drain electrode both at the blocking state and after ion strike. The TCAD simulation results show that the SET peak drain current of the BP-HEMT is significantly dropped to 0.49 A/mm from 4.17 A/mm of the conventional HEMT with a linear energy transfer (LET) of 0.6 pC/μm, and the BV is significantly increased to 1318.3 V from 175.2 V, as well as the Ron decreases by 11.1%.

Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Abstract The skin is intrinsically a cell-membrane-compartmentalized hydrogel with high mechanical strength, potent antimicrobial ability, and robust immunological competence, which provide multiple protective effects to the body. Methods capable of preparing hydrogels that can simultaneously mimic the structure and function of the skin are highly desirable but have been proven to be a challenge. Here, dual structurally and functionally skin-mimicking hydrogels are generated by crosslinking cell-membrane compartments. The crosslinked network is formed via free radical polymerization using olefinic double bond-functionalized extracellular vesicles as a crosslinker. Due to the dissipation of stretching energy mediated by vesicular deformation, the obtained compartment-crosslinked network shows enhanced mechanical strength compared to hydrogels crosslinked by regular divinyl monomers. Biomimetic hydrogels also exhibit specific antibacterial activity and adequate ability to promote the maturation and activation of dendritic cells given the existence of numerous extracellular vesicle-associated bioactive substances. In addition, the versatility of this approach to tune both the structure and function of the resulting hydrogels is demonstrated through introducing a second network by catalyst-free click reaction-mediated crosslinking between alkyne-double-ended polymers and azido-decorated extracellular vesicles. This study provides a platform to develop dual structure- and function-controllable skin-inspired biomaterials.

Abstract The metal-support interactions (MSI) could greatly determine the electronic properties of single-atom catalysts, thus affecting the catalytic performance. However, the typical approach to regulating MSI usually suffers from interference of the variation of supports or sacrificing the stability of catalysts. Here, we effectively regulate the site-specific MSI of Ir single atoms anchored on Ni layered double hydroxide through an electrochemical deposition strategy. Cathodic deposition drives Ir atoms to locate at three-fold facial center cubic hollow sites with strong MSI, while anodic deposition drives Ir atoms to deposit onto oxygen vacancy sites with weak MSI. The mass activity and intrinsic activity of Ir single-atom catalysts with strong MSI towards oxygen evolution reaction are 19.5 and 5.2 times that with weak MSI, respectively. Mechanism study reveals that the strong MSI between Ir atoms and the support stimulates the activity of Ir sites by inducing the switch of active sites from Ni sites to Ir sites and optimizes the adsorption strength of intermediates, thereby enhancing the activity.

Abstract Due to the rising need for clean and renewable energy, green materials including biochar are becoming increasingly popular in the field of energy storage and conversion. However, the lack of highly active and stable electrode materials hinders the development of stable energy supplies and efficient hydrogen production devices. Herein, we fabricated stable, conductive, and multifunctional chitosan microspheres by a facile emulsion crosslinking solution growth and hydrothermal sulphuration methods as multifunctional electrodes for overall water splitting driven by supercapacitors. This material possessed three-dimensional layered conductors with favorable heterojunction interface, ample hollow and porous structures. It presented remarkably enhanced electrochemical and catalytic activity for both supercapacitors and overall water electrolysis. The asymmetric supercapacitors based on chitosan biochar microsphere achieved high specific capacitance (260.9 F g−1 at 1 A g−1) and high energy density (81.5W h kg−1) at a power density of 978.4 W kg−1. The chitosan biochar microsphere as an electrode for electrolyze only required a low cell voltage of 1.49 V to reach a current density of 10 mA cm−2, and achieved excellent stability with 30 h continuous test at 20 mA cm−2. Then, we assembled a coupled energy storage device and hydrogen production system, the SCs as a backup power source availably guaranteed the continuous operation of overall water electrolysis. Our study provides valuable perspectives into the practical design of both integrated biochar-based electrode materials and coupled energy storage devices with energy conversion and storage in practical. Graphical Abstract

Abstract Osteoarthritis (OA) is the most common degenerative joint disease. Currently, no satisfactory pharmacological treatment exists for OA. The potential anti-inflammatory properties of Dihydrotanshinone I (DHT) have been reported, but its effects on OA are unclear. In this study, we assess the impact of DHT on the viability of human chondrocytes in vitro. We then use a guinea pig model to investigate the effects of DHT on knee osteoarthritis progression. Twelve-week-old Dunkin Hartley guinea pigs spontaneously developing OA were intraperitoneally injected with different doses of DHT for eight weeks. Micro-CT analysis was performed on the subchondral bone in the knee, and histological assessment of the knee joint was done using stained sections, the ratio of hyaline to calcified cartilage, and Mankin scores. DHT successfully restored IL-1β-induced decreases in cell viability in human primary chondrocytes. In the guinea pig model, intraperitoneal injections of DHT ameliorated age-induced OA, effectively reduced the expression level of two cartilage metabolism-related genes (ADAMTS4 and MMP13) and decreased the inflammatory biomarker IL-6 in the serum of guinea pigs developing spontaneous osteoarthritis. These findings demonstrate DHT’s protective effects on chondrocytes and suggest that it alleviates cartilage degradation and proteoglycan loss in OA.

In order to solve the problem of how to quickly and accurately obtain the location information of self-organizing networks or target objects in the narrow and closed battlefield environment, such as the enemy command center, cabins, and underground buildings, this paper proposes a positioning algorithm based on the communication module provided by individual intelligent terminal equipment, we use the support of hardware devices such as visible light sensors, and study the communication signal fingerprint of swarm intelligence perception, combined with image matching algorithm. This algorithm mainly communicates with fingerprint data to achieve preliminary positioning, combines a weighted average algorithm of fused images and attitude sensors, and uses swarm intelligence perception to supplement and update positioning data. By adjusting the image matching strategy, while maintaining accuracy, compared to a single image matching positioning algorithm, it reduces computational power requirements and improves real-time performance in battlefield environments with complex communication conditions. Compared with the standard WKNN (Weighted K-Nearest Neighbors) algorithm, it improves the stability of localization in complex environments, and the average localization error is less than 1.72 m, reducing the error by about 50%.

Abstract Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs. In this study, we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulation-specific gene expression between cartilage with macroscopically confirmed osteoarthritis (n = 5) and cartilage without osteoarthritis (n = 5) from the interphalangeal joints of five donors. Of 105 142 cells, we identified 13 subpopulations, including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes. Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage. Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage. In these two subpopulations from osteoarthritic cartilage, the ferroptosis pathway was enriched, and expression of iron overload-related genes, e.g., FTH1, was elevated. To verify these findings, we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study. Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis (odds ratio = 1.07, 95% confidence interval: 1.02–1.11) among participants (n = 332 668) in UK Biobank. High levels of serum ferritin (encoded by FTH1), a biomarker of body iron overload, were significantly associated with a high prevalence of hand osteoarthritis among participants (n = 1 241) of Xiangya Osteoarthritis Study (P-for-trend = 0.037). In conclusion, our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis, providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.

Abstract Aims To compare measurement properties of EQ-5D-5L and SF-6DV2 in university staff and students in China. Methods A total of 291 staff and 183 undergraduates or postgraduates completed the two instruments assigned in a random order. The health utility scores (HUS) of EQ-5D-5L and SF-6DV2 were calculated using the respective value sets for Chinese populations. The agreement of HUSs was examined using intraclass correlation coefficients (ICC) and Bland-Altman plot. Convergent validity of their HUSs and similar dimensions were assessed using Spearman’s correlation coefficient. Known-group validity of the HUSs and EQ-VAS score was assessed by comparing the scores of participants with and without three conditions (i.e., disease, symptom or discomfort, and injury), as well as number of any of the three conditions; their sensitivity was also compared. Results The ICCs between the two HUSs were 0.567 (staff) and 0.553 (students). Bland-Altman plot found that EQ-5D-5L HUSs were generally higher. Strong correlation was detected for two similar dimensions (pain/discomfort of EQ-5D-5L and pain of SF-6DV2; anxiety/depression of EQ-5D-5L and mental health of SF-6DV2) in both samples. The correlation between the two HUSs were strong (0.692 for staff and 0.703 for students), and were stronger than their correlations with EQ-VAS score. All the three scores could discriminate the difference in three known-groups (disease, symptom or discomfort, number of any of the three conditions). The two HUSs were more sensitive than EQ-VAS score; and either of them was not superior than the other. Conclusions Both EQ-5D-5L and SF-6DV2 HUSs have acceptable measurement properties (convergent validity, known-groups validity, sensitivity) in Chinese university staff and students. Nevetheless, only EQ-5D-5L (PD and AD) and SF-6DV2 (PN and MH) showed indicated good convergent validity as expected. Two types of HUSs cannot be used interchangeably, and each has its own advantages in sensitivity.

Bacterial community is strongly associated with activated sludge performance, but there still remains a knowledge gap regarding the rare bacterial community assembly and their influence on the system performance in industrial wastewater treatment plants (IWWTPs). Here, we investigated bacterial communities in 11 full-scale IWWTPs with similar process designs, aiming to uncover ecological processes and functional traits regulating abundant and rare communities. Our findings indicated that abundant bacterial community assembly was governed by stochastic processes; thereby, abundant taxa are generally present in wastewater treatment compartments across different industrial types. On the contrary, rare bacterial taxa were primarily driven by deterministic processes (homogeneous selection 61.9%-79.7%), thus they only exited in specific IWWTPs compartments and wastewater types. The co-occurrence networks analysis showed that the majority of keystone taxa were rare bacterial taxa, with rare taxa contributing more to network stability. Furthermore, rare bacteria rather than abundant bacteria in the oxic compartment contributed more to the degradation of xenobiotics compounds, and they were main potential drivers of pollutant removal. This study demonstrated the irreplaceable roles of rare bacterial taxa in maintaining system performance of IWWTPs, and called for environmental engineers and microbial ecologists to increase their attention on rare biosphere.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with unknown etiology and treatment options for it were limited. Whether Gastroesophageal reflux disease (GERD) could affect the occurrence of IPF remains unclear. Methods : Using available data from FINNGEN and IEU OpenGWAS, we performed Two-sample mendelian randomization (MR) to explore the causal relationship between GERD and IPF. Results: Using 65 GERD-related SNPs, we found the association between GERD and the risk of IPF was not statistically significant with IVW approach (OR = 1.20, 95% CI = 0.84-1.70, p = .32), MR-Egger regression (OR = 1.65, 95% CI = 0.19-14.43, p = .65) and weighted median approaches (OR = 1.44, 95% CI = 0.94-2.23, p = .09). However, heterogeneity was observed with MR-Egger ( p = .001) and IVW ( p = .001) analysis. Similar results were obtained with MR-PRESSO (global heterogeneity test p value

ABSTRACT: Primary hepatocytes (PH) have been widely used in metabolic and disease-resistance mechanism research. However, hepatocyte isolation (HI) remains challenging in ducks. This study aimed to explore embryonic growth and the effect of embryonic age (EA) on the quantitative and functional characteristics of PH in ducks. For embryonic growth, the size and weight of the embryo and liver were determined from 6 to 28 EA (E6–E28, similar below). As EA increased, the corresponding size and weight grew significantly. Specifically, embryonic length varied from 12.5 mm to 133.0 mm, and liver width varied from 2.0 mm to 26.2 mm. Embryonic weight ranged from 0.259 g to 53.58 g, and liver weight ranged from 0.007 g to 1.765 g. Liver index initially decreased and then increased with a ratio ranging from 1.06 to 3.29%. For quantitative and functional characteristics, they were determined from E6 to E22, as there were no obvious liver features before E6 and few cells obtained after E22. The number of cells isolated in liver increased from E6 to E16 and then sharply decreased from E16 to E22. The viability remained relatively stable from E6 to E10 and then decreased from E12 to E22. The comprehensive intensity of hepatic glycogen was stronger at E8 and E14. Albumin expression increased markedly from E6 to E18 by qPCR, and the overall albumin expression was stronger at E8 and E14 by immunofluorescence assay. Hepatocyte purity exceeded 90% except for E20 and E22. During culture, cell clusters appeared after 24-h culture, which were identified as nonhepatocytes. The growth curve showed an initial increase in cell quantity followed by a decrease, another increase, and then remaining stable. In conclusion, EA had a significant effect on the quantitative and functional characteristics of PH, and the suitable EA for HI were E8 and E14. Considering better operability and quantity, E14 was the optimal EA, laying a solid foundation for further hepatocyte purification, nutrient metabolism, and disease-resistance mechanism explorations in ducks.

In this study, the mating system of the endangered aquatic fern Ceratopteris thalictroides in China was investigated using microsatellite markers. The estimates of the multilocus outcrossing rate (tm) and single-locus outcrossing rate (ts) were high at the species level (tm = 0.701 and ts = 0.595, respectively), indicating that C. thalictroides is a predominantly outcrossing species. Negative F (inbreeding coefficient of the maternal parents) values (-0.137) at the species level indicated an excess of heterozygotes and low inbreeding in the populations analyzed. Our investigation revealed that some of the natural and ex situ conservation populations of C. thalictroides have a prolific capacity for vegetative growth. The results showed that the homosporous pteridophyte C. thalictroides in China predominantly favors gametophytic crossing with a certain level of inbreeding along with vegetative growth. Ten populations have been established for ex situ conservation in Wuhan, China, with a survival rate of more than 90%, and mature spores were collected from them. Several factors, including high dispersal of spores and gametophytes by flowing water, high gene flow, and the wide distribution of the species in China, with the occurrence of some large populations, may have resulted in a high outcrossing rate in Chinese C. thalictroides. The high outcrossing rate of C. thalictroides showed that ex situ plantings are most suitable for enhancing possible mixing of the different populations, thus minimizing inbreeding.

Introduction: Ovarian cancer remains to be a significant cause of global cancer-related mortality. In recent years, there has been a surge of studies in investigating the application of nanomaterials in the diagnosis and treatment of ovarian cancer. This study aims to conduct a comprehensive bibliometric analysis regarding nanomaterial-based researches on ovarian cancer to evaluate the current state and emerging patterns in this field.Methods: A thorough literature search on the Web of Science Core Collection database was conducted to identify articles focused on nanomaterial-based ovarian cancer researches. The studies that met the inclusion criteria were selected for further analysis. VOSviewer and CiteSpace were applied for the bibliometric and visual analyses of the selected publications.Results: A total of 2,426 studies were included in this study. The number of annual publications showed a consistent upward trend from 2003 to 2023. Notably, China, the United States, and India have emerged as the leading contributors in this field, accounting for 37.39%, 34.04%, and 5.69% of the publications, respectively. The Chinese Academy of Sciences and Anil K. Sood were identified as the most influential institution and author, respectively. Furthermore, the International Journal of Nanomedicine was the most frequently cited journal. In terms of the research focus, significant attention has been directed towards nanomaterial-related drug delivery, while the exploration of immunogenic cell death and metal-organic frameworks represented recent areas of interest.Conclusion: Through comprehensive analyses, an overview of current research trends and emerging areas of interest regarding the application of nanomaterials in ovarian cancer was illustrated. These findings offered valuable insights into the status and future directions of this dynamic field.