Ruegeria marisflavi sp. nov. and Ruegeria aquimaris sp. nov., isolated from seawater of the Yellow Sea.

Two novel Gram-stain-negative, aerobic, non-motile and rod-shaped bacteria, designated as WL0004T and XHP0148T, were isolated from seawater samples collected from the coastal areas of Nantong and Lianyungang, PR China, respectively. Both strains were found to grow at 10-42 °C (optimum, 37 °C) and with 2.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Strain WL0004T grew at pH 6.0-9.0 (optimum, pH 7.0-8.0), while XHP0148T grew at pH 6.0-10.0 (optimum, pH 7.0-8.0). The major cellular fatty acids (>10 %) of both strains included summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c). In addition, strain WL0004T contained 11-methyl C18 : 1 ω7c and strain XHP0148T contained C12 : 0 3-OH. The respiratory quinone of both strains was ubiquinone-10. The G+C content of genomic DNA of strains WL0004T and XHP0148T were 62.5 and 63.0 mol%, respectively. Strains WL0004T and XHP0148T showed the highest 16S rRNA gene sequence similarity to Ruegeria pomeroyi DSS-3T (99.4 and 99.0 %, respectively), and the 16S rRNA gene-based phylogenetic analysis indicated that the two strains were closely related to members of the genus Ruegeria. The average nucleotide identity and digital DNA-DNA hybridization values among the two strains and type strains of the genus Ruegeria were all below 95 and 70 %, respectively, and the phylogenetic tree reconstructed from the bac120 gene set indicated that the two strains are distinct from each other and the members of the genus Ruegeria. Based on this phenotypic and genotypic characterization, strains WL0004T (=MCCC 1K07523T=JCM 35565T=GDMCC 1.3083T) and XHP0148T (=MCCC 1K07543T=JCM 35569T=GDMCC 1.3089T) should be recognized as representing two novel species of the genus Ruegeria and the names Ruegeria marisflavi sp. nov. and Ruegeria aquimaris sp. nov. are proposed, respectively.

Description of Nesterenkonia aerolata sp. nov., an actinobacterium isolated from air of manufacturing shop in a pharmaceutical factory.

During our studies on the microorganism diversity from air of manufacturing shop in a pharmaceutical factory in Shandong province, China, a Gram-stain-positive, aerobic, cocci-shaped bacterium, designated LY-0111T, was isolated from a settling dish. Strain LY-0111T grew at temperature of 10-42 °C (optimum 35 °C), pH of 5.0-10.0 (optimum pH 7.0) and NaCl concentration of 1-12% (optimum 0.5-3%, w/v). Based on the 16S rRNA gene sequence analysis, the strain shared the highest sequence similarities to Nesterenkonia halophila YIM 70179T (96.2%), and was placed within the radiation of Nesterenkonia species in the phylogenetic trees. The genome of the isolate was sequenced, which comprised 2,931,270 bp with G + C content of 66.5%. A supermatrix tree based on the gene set bac120 indicated that LY-0111T was close related to Nesterenkonia xinjiangensis YIM 70097T (16S rRNA gene sequence similarity 95.3%). Chemotaxonomic analysis indicated that the main respiratory quinones were MK-7, MK-8, and MK-9, the predominant cellular fatty acids were anteiso-C15:0 and iso-C15:0, and the major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. According to the phenotypic, chemotaxonomic and phylogenetic features, strain LY-0111T is considered to represent a novel species, for which the name Nesterenkonia aerolata sp. nov. is proposed. The type strain is LY-0111T (= JCM 36375T = GDMCC 1.3945T). In addition, Nesterenkonia jeotgali was proposed as a later synonym of Nesterenkonia sandarakina, according to the ANI (96.8%) and dDDH (72.9%) analysis between them.

Bioactive VS4-based sonosensitizer for robust chemodynamic, sonodynamic and osteogenic therapy of infected bone defects.

BACKGROUND: Most bone defects caused by bone disease or trauma are accompanied by infection, and there is a high risk of infection spread and defect expansion. Traditional clinical treatment plans often fail due to issues like antibiotic resistance and non-union of bones. Therefore, the treatment of infected bone defects requires a strategy that simultaneously achieves high antibacterial efficiency and promotes bone regeneration. RESULTS: In this study, an ultrasound responsive vanadium tetrasulfide-loaded MXene (VSM) Schottky junction is constructed for rapid methicillin-resistant staphylococcus aureus (MRSA) clearance and bone regeneration. Due to the peroxidase (POD)-like activity of VS4 and the abundant Schottky junctions, VSM has high electron-hole separation efficiency and a decreased band gap, exhibiting a strong chemodynamic and sonodynamic antibacterial efficiency of 94.03%. Under the stimulation of medical dose ultrasound, the steady release of vanadium element promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The in vivo application of VSM in infected tibial plateau bone defects of rats also has a great therapeutic effect, eliminating MRSA infection, then inhibiting inflammation and improving bone regeneration. CONCLUSION: The present work successfully develops an ultrasound responsive VS4-based versatile sonosensitizer for robust effective antibacterial and osteogenic therapy of infected bone defects.

Description of Limnobaculum eriocheiris sp. nov., an intestinal bacterium of Eriocheir sinensis, and reclassification of the genera Jinshanibacter and Insectihabitans as Limnobaculum.

A Gram-stain-negative, aerobic, non-motile and rod-shaped strain, designated LJY008T, was isolated from the intestinal of Eriocheir sinensis in Pukou base of Jiangsu Institute of Freshwater Fisheries. Strain LJY008T could grow at 4-37 â„ƒ (optimum, 30 â„ƒ), pH 6.0-8.0 (optimum, pH 7.0), and with 1.0-6.0% NaCl (w/v; optimum, 1.0%). Strain LJY008T shared highest 16S rRNA gene sequence similarity with Jinshanibacter zhutongyuii CF-458T (99.3%), followed by J. allomyrinae BWR-B9T (99.2%), Insectihabitans xujianqingii CF-1111T (97.3%), and Limnobaculum parvum HYN0051T (96.7%). The major polar lipids include phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The only respiratory quinone was Q8, and the main fatty acids (> 10%) were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), summed feature 8 (C18:1ω7c), and C14:0. The genome-based phylogenies showed that strain LJY008T was closely associated with members of the genus Jinshanibacter, Insectihabitans, and Limnobaculum. The average nucleotide identities and average amino acid identities (AAI) among strain LJY008T and closely related neighbours were all below 95%, and the digital DNA-DNA hybridization values among them were all below 36%. The genomic DNA G + C content of strain LJY008T was 46.1%. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain LJY008T represents a novel species of the genus Limnobaculum, for which the name Limnobaculum eriocheiris sp. nov. is proposed. The type strain is LJY008T (= JCM 34675T = GDMCC 1.2436T = MCCC 1K06016T). In addition, the genera Jinshanibacter and Insectihabitans were reclassified as Limnobaculum, because there was no significant genome-scale divergence or diagnosable difference on phenotypic and chemotaxonomic traits, such as strains of Jinshanibacter and Insectihabitans sharing AAI values of 93.88-94.96%.

Comparison of Outcomes Following TiRobot-Assisted Sacroiliac Screw Fixation with Bone Grafting and Traditional Screw Fixation without Bone Grafting for Unstable Osteoporotic Sacral Fracture: A Single-Center Retrospective Study of 33 Patients.

BACKGROUND This retrospective study from a single center aimed to compare patient outcomes following TiRobot-assisted sacroiliac screw fixation and bone grafting with traditional screw fixation without bone grafting in 33 patients with unstable osteoporotic sacral fracture (UOSF). MATERIAL AND METHODS Patients with UOSF were included and divided into 2 groups: a TiRobot-assisted surgical group with 18 patients (robot-aided sacroiliac screw fixation and bone grafting) and a standard surgical group with 15 patients (free-hand screw fixation without bone grafting). T values of bone mineral density (BMD) £-2.5 standard deviation (SD) were diagnosed as osteoporosis. Screw positioning and fracture healing time were evaluated. Functional outcomes were investigated at the final follow-up. RESULTS There were no statistically significant differences in screw positioning; however, there were satisfactory positioning rates in 94.4% (17/18) of patients in the TiRobot-assisted surgical group and 73.3% (11/15) in the standard surgical group. The advantages with TiRobot on surgical time of screw placement, fluoroscopy frequency, and total drilling times were noted (P=0.000). The nonunion rates were 5.6% (1/18) in the TiRobot-assisted surgical group and 33.3% (5/15) in the standard group (P=0.039). Healing time in the union cases had a significant difference (P=0.031). Functional outcome scores in the TiRobot-assisted surgical group were superior to that in the standard group (P=0.014). CONCLUSIONS The findings showed that TiRobot-assisted sacroiliac screw fixation and bone grafting was a safe and effective surgical treatment option that had a reduced radiation dose and improved fracture healing, when compared with standard screw fixation without bone grafting.

Disparities in unmet health service needs among people with disabilities in China.

BACKGROUND: Extensive research has explored disparities in access to health care between people with and without disabilities, but much less is understood about disparities and associated factors within the disabled population. OBJECTIVE: The aim of this study was to examine differences in the prevalence of unmet health-care needs by residential status (hukou status) and disability type among people with disabilities. METHODS: Our data were from the National Survey on Basic Public Service Delivery of Persons with Disabilities. The analysis sample included a nationally representative sample of 9 642 112 adults (aged 16+ years) with disabilities. Associated factors were obtained at both individual level and community level. Cross-sectional multivariable logistic regression analyses were conducted to compare unmet medical, care, rehabilitation and accessibility needs among people with different residential statuses and different types of disabilities. RESULTS: The estimated prevalence of unmet medical, care, rehabilitation and accessibility needs is 15.4%, 10.2%, 45.6% and 13.7%, respectively. Rural hukou was associated with an important 13-40% increase in unmet health-care needs for people with disabilities in China. These rural-urban disparities in unmet health service needs can be partly explained by community-level factors, including access to facilities, social participation and health professionals. Disparities across the type of disability were smaller, but on average, people with multiple disabilities appeared to have the highest rates of unmet care, medical and accessibility needs, whereas those with physical disability had the highest unmet rehabilitation need. CONCLUSIONS: Differences by residential status and impairment type were evident in all types of unmet health service needs. Targeted policy designs that meet the needs for justice and equality of people with disabilities are advisable. Public health and policy efforts are required to improve access to health service and meet the needs of people with disabilities, especially in rural practices and for particular disability groups.

NADPH Oxidase ClNOX2 Regulates Melanin-Mediated Development and Virulence in Curvularia lunata.

The role of NADPH oxidases (NOXs) in pathogenesis and development in the Curvularia leaf spot agent Curvularia lunata remains poorly understood. In this study, we identified C. lunata ClNOX2, which localized to the plasma membrane and was responsible for reactive oxygen species (ROS) generation. Scavenging the ROS production inhibited the conidial germination and appressorial formation. The ClNOX2 and ClBRN1 deletion mutants were defective in 1,8-dihydroxynaphthalene (DHN) melanin accumulation, appressorial formation, and cellulase synthesis and exhibited lower virulence. However, disruption of the ClNOX2 and ClBRN1 genes facilitated hyphal growth, enhanced stress adaptation to cell-wall-disrupting agents, and promoted developmental processes such as conidiation, conidial germination, and pseudothecium and ascus formation. Interestingly, loss of ClM1, the cell wall integrity (CWI) mitogen-activated protein kinase gene in C. lunata, led to morphology and pathogenicity phenotypes similar to ClNOX2 and ClBRN1 deletion mutants such as abnormal conidia, fewer appressoria, less melanin, increased hyphal growth, and enhanced tolerance to Congo red (CR). These results indicated that the ClNOX2 gene plays an important role in C. lunata development and virulence via regulating intracellular DHN melanin biosynthesis. Quantitative reverse-transcription PCR revealed that the ClNOX2-related ROS signaling pathway and ClM1-mediated CWI signaling pathway are cross-linked in regulating DHN melanin biosynthesis. Our findings provide new insights into how ClNOX2 participates in pathogenesis and development in hemibiotrophic plant fungal pathogens.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Virulence and Molecular Diversity in the Kabatiella zeae Population Causing Maize Eyespot in China.

Maize eyespot, caused by Kabatiella zeae, has become a major yield-limiting factor in maize planting areas in northeast China. Limited information is available on pathotypes, virulence, and the genetic diversity of the K. zeae population. We analyzed virulence and genetic diversity of 103 K. zeae isolates collected from six provinces in China with differential hosts and the amplified fragment length polymorphism (AFLP) technique, respectively. To evaluate the virulence, 103 isolates were inoculated on nine differential hosts (maize inbred lines)-E28, Shen137, Qi319, B73, Danhuang34, Zi330, Mo17, Huangzaosi, and CN165-and grouped into 23 pathotypes and three virulence groups according to the coded triplet nomenclature system on differential hosts. AFLP analysis resolved the set of isolates into four genetic diversity clusters (DICE similarity values of 76%). Genetic variation of K. zeae among and between pathotypes revealed that the pathogen population had a high genotypic diversity. The correlation between pathotypes, virulence, and genetic diversity grouping was low. A correlation between AFLP groups and geographic locations was detected.

Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

Similar survival between uncemented and cemented fixation prostheses in total knee arthroplasty: a meta-analysis and systematic comparative analysis using registers.

PURPOSE: The purpose of this analysis was to determine whether uncemented total knee arthroplasty performs as well as cemented total knee arthroplasty. METHODS: We searched PubMed, MEDLINE, and EMBASE, and major orthopaedic journals. This search was performed for the years from 1980 to the present. Randomised controlled trials and observational studies comparing cemented and uncemented fixation were identified. Effective data were pooled for meta-analysis. A systematic search was carried out using the EFORT website to identify the relevant arthroplasty registers. RESULTS: Nine studies were included in the meta-analysis. The combined odds ratio for failure of the implant due to aseptic loosening for the uncemented group over 5 and 10 years were 3.41 (p = 0.0001) and 4.73 (p = 0.0002), respectively. Subgroup analysis of data when design-related failed total knee arthroplasty (TKA)s were excluded showed no difference between the groups for odds of aseptic loosening (n.s.). There was no difference between the groups with respect to infection (n.s.). Pooled outcome of register data revealed that uncemented knees had a higher revision rate than cemented knees. CONCLUSIONS: The important finding from the current study is that there is no evidence to support that fixation techniques alone affect the durability of a total knee arthroplasty when design-related failure in TKAs was excluded. The way of fixation is not relevant to the incidence of infection. LEVEL OF EVIDENCE: IV.

How economic development affects healthcare access for people with disabilities: A multilevel study in China.

Meeting the healthcare needs of people with disabilities is an important challenge in achieving the central promise of "leave no one behind" during the Sustainable Development Goals era. In this study, we describe the accessibility of healthcare for people living with disabilities, as well as the potential influences of individuals' socioeconomic status and regional economic development. Our data covered 324 prefectural cities in China in 2019 and captured the access to healthcare services for people with disabilities. First, we used linear probability regression models to investigate the association between individual socioeconomic status, including residence, poverty status, education, and healthcare access. Second, we conducted an ecological analysis to test the association between prefectural economic indicators, including GDP (gross domestic product) per capita, urbanization ratio, average years of education, Engel's coefficient, and the overall prevalence of access to healthcare for people with disabilities within prefectures. Third, we used multilevel regression models to explore the association between the individual's socio-economic status, prefectural economic indicators, and access to healthcare at the individual level for people with disabilities. The results showed, first, that higher individual socioeconomic status (urban residence or higher educational level) was associated with better access to healthcare for people with disabilities. Second, regional economic indicators were positively associated with access to healthcare at the aggregate and individual levels. This study suggests that local governments, particularly in low- and middle-income countries, should promote economic development and conduct poverty alleviation policies to improve healthcare access for disadvantaged groups.

A Janus-ROS Healing System Promoting Infectious Bone Regeneration via Sono-Epigenetic Modulation.

Elimination of bacterial infections and simultaneously promoting osteogenic differentiation are highly required for infectious bone diseases. Massive reactive oxygen species (ROS) can damage cells, while low ROS concentrations as a molecular signal can regulate cellular fate. In this study, a Janus-ROS healing system is developed for infectious bone regeneration. An alendronate (ALN)-mediated defective metal-organic framework (MOF) sonosensitizer is prepared, which can effectively clear Methicillin-resistant Staphylococcus aureus (MRSA) infections and promote osteogenic differentiation under differential ultrasonic irradiation. In the presence of zirconium-phosphate coordination, the ALN-mediated porphyrin-based MOF (HN25) with a proper defect has great sonodynamic antibacterial efficiency (98.97%, 15 min) and bone-targeting ability. Notably, under low-power ultrasound irradiation, HN25 can increase the chromatin accessibility of ossification-related genes and FOXO1 to promote bone repair through low ROS concentrations. Animal models of paravertebral infection, fracture with infection, and osteomyelitis demonstrate that HN25 successfully realizes the targeted and potent repair of various infectious bone tissues through rapid MRSA elimination, inhibiting osteoclast activity and promoting bone regeneration. The results show that high catalytic efficiency and bioactive MOF can be constructed using pharmaceutical-mediated defect engineering. The Janus-ROS treatment is also a promising therapeutic mode for infectious tissue regeneration.

Stomatohabitans albus gen. nov., sp. nov., an oral living facultative anaerobic actinobacteria isolated form Steller sea lion, and proposal of Stomatohabitantaceae fam. nov. and Stomatohabitantales ord. nov.

Two novel actinobacteria, designated as SYSU M7M538T and SYSU M7M531, were isolated from oral of Eumetopias jubatus in Zhuhai Chimelong Ocean Kingdom, China. The cells of these microorganisms stained Gram-positive and were rod shaped. These strains were facultative anaerobic, and catalase-positive. Optimal growth occurred at 37 °C and pH 7.0 over 7 days of cultivation. Both strains possessed diphosphatidylglycerol, phosphatidylglycerol and phosphocholine as the major polar lipids. The main menaquinone was MK-9(H4). The major fatty acids were C16:0, C17:1w8c, C17:0, C18:1w9c and C18:0. Analyses of genome sequences revealed that the genome size of SYSU M7M538T was 2.1 Mbp with G + C content of 52.5 %, while the genome size of SYSU M7M531 was 2.3 Mbp with G + C content of 52.7 %. The ANI and 16S rRNA gene analysis results showed that the pairwise similarities between the two strains and other recognized Nitriliruptoria species were less than 64.9 % and 89.0 %, respectively. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strains SYSU M7M538T and SYSU M7M531 formed a well-separated phylogenetic branch distinct from other orders of Nitriliruptoria. Based on the data presented here, these two strains are considered to represent a novel species of a novel genus, for which the name Stomatohabitans albus gen. nov., sp. nov., with the type strain SYSU M7M538T (=KCTC 59113T = GDMCC 1.4286T), are proposed. We also propose that these organisms represent a novel family named Stomatohabitantaceae fam. nov. of a novel order Stomatohabitantales ord. nov.

Ultrasound-controlled MXene-based Schottky heterojunction improves anti-infection and osteogenesis properties.

Background: The current clinical treatment of osteomyelitis is limited by the emergence of drug-resistant bacteria, which often leads to the failure of traditional antibiotic treatment and large bone defects. Sonodynamic therapy (SDT) is a new strategy that is widely used to overcome the problem of bacterial resistance to antibiotic therapy as well as poor tissue penetration using near-infrared light in photodynamic therapy (PDT). Therefore, it is necessary to develop a new sonosensitizer that can kill bacteria and promote bone repair. Methods: Herein, we developed a sonosensitizer, porphyrin metal-organic framework (HNTM), with a Schottky junction modified by Ti3C2 nanosheets (HN-Ti3C2) for highly efficient sonodynamic therapy of osteomyelitis and bone regeneration. Results: Ti3C2 greatly improves the acoustic catalytic performance by rapidly transferring the charge carriers generated by HNTM under ultrasound (US) irradiation, which killing drug-resistant bacteria through the generation of large amounts of reactive oxygen species (ROS). And HN-Ti3C2 shows excellent 99.75% antibacterial effectiveness against MRSA. In addition, HN-Ti3C2 generates a sonocurrent under low-intensity US to promote the repair of bone defects for a long time period. Mechanistic research using CCK-8 and RNA-seq showed that HN-Ti3C2 nanocomposites can promote the proliferation of stem cells by regulating the cell cycle, DNA replication, and apoptosis. In addition, after low-intensity US irradiation, HN-Ti3C2 promotes osteogenic differentiation via some key signaling pathways, including the calcium, Wnt, and TGF-beta signaling pathways, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). In a MRSA-infected rat tibial osteomyelitis model, HN-Ti3C2 successfully eliminated the infection and significantly improved bone regeneration under US irradiation. Conclusion: This study indicates that engineered HN-Ti3C2 is a distinctive nanocomposite for successful osteomyelitis treatment.

The effect of a disability-targeted cash transfer program on universal health coverage and universal access to education: a nationwide cohort study of Chinese children and adolescents with disabilities.

Background: To achieve improved outcomes for children and adolescents with disabilities, it is central to have universal health coverage (UHC) and universal access to education. This study investigates whether a disability-targeted cash transfer (CT) program is associated with improved access to healthcare and education for children and adolescents with disabilities. Methods: We used nationwide survey data of two million children and adolescents living with disabilities, who aged 8-15 years when entering the cohort between January 1, 2015, and December 31, 2019. With a quasi-experimental study design, we compared the outcomes between CT beneficiaries who newly received CT benefits during the study period and non-beneficiaries who were disabled but never received CT using logistic regressions after propensity score matching with a 1:1 ratio. Outcomes of interest were utilization of rehabilitation services in the past year, medical treatment if the individual had illness in the past two weeks, school attendance if not in school at the start of the study, and reported financial hardship to access these services. Findings: Of the total cohort, 368,595 children and adolescents fit the inclusion criteria, including 157,707 new CT beneficiaries and 210,888 non-beneficiaries. After matching, CT beneficiaries showed 2.27 (95% confidence interval [CI]: 2.23, 2.31) higher odds of utilizing rehabilitation services and 1.34 (95% CI: 1.23, 1.46) higher odds of getting medical treatment compared to non-beneficiaries. CT benefits were also significantly associated with less report of financial barrier to access rehabilitation services (odds ratio [OR]: 0.63, 95% CI: 0.60, 0.66) and medical treatment (OR: 0.66, 95% CI: 0.57, 0.78). Moreover, CT program was associated with higher odds of school attendance (OR: 1.99, 95% CI: 1.85, 2.15) and lower odds of reporting financial difficult to access education (OR: 0.41, 95% CI: 0.36, 0.47). Interpretation: Our results suggest that the receipt of CT was associated with improved access to health and educational resources. This finding provides supporting evidence for the identification of efficient and feasible interventions to move toward UHC and universal education under the Sustainable Development Goals. Funding: This research was supported by Sanming Project of Medicine in Shenzhen (NO.SZSM202111001), China National Natural Science Foundation (Grant/Award Number: 72274104, 71904099) and Tsinghua University Spring Breeze Fund (20213080028).

Heterostructured piezocatalytic nanoparticles with enhanced ultrasound response for efficient repair of infectious bone defects.

Infection of bone defects remains a challenging issue in clinical practice, resulting in various complications. The current clinical treatments include antibiotic therapy and surgical debridement, which can cause drug-resistance and potential postoperative complications. Therefore, there is an urgent need for an efficient treatment to sterilize and promote bone repair in situ. In this work, an ultrasound responsive selenium modified barium titanate nanoparticle (Se@BTO NP) was fabricated, which exhibited significant antibacterial and bone regeneration effects. Selenium nanoparticle (Se NP) was modified on the surface of barium titanate nanoparticle (BTO NP) to form heterostructure, which facilitated the second distribution of piezo-induced carriers under ultrasound (US) irradiation and improved the separation of electron-hole pairs. The Se@BTO NPs exhibited remarkable antibacterial efficiency with an antibacterial rate of 99.23 % against Staphylococcus aureus (S.aureus) and significantly promoted the osteogenic differentiation under ultrasound irradiation. The in vivo experiments exhibited that Se@BTO NPs successfully repaired the femoral condylar bone defects of rats infected by S.aureus, resulting in significant promotion of bone regeneration. Overall, this work provided an innovative strategy for the utilization of US responsive nanomaterials in efficient bacteria elimination and bone regeneration. STATEMENT OF SIGNIFICANCE: Infectious bone defects remain a challenging issue in clinical practice. Current antibiotic therapy and surgical debridement has numerous limitations such as drug-resistance and potential complications. Herein, we designed an innovative ultrasound responsive selenium modified barium titanate nanoparticle (Se@BTO NP) to achieve efficient non-invasive bacteria elimination and bone regeneration. In this work, Se@BTO nanoparticles can enhance the separation of electrons and holes, facilitate the transfer of free carriers due to the cooperative effect of ultrasound induced piezoelectric field and heterojunction construction, and thus exhibit remarkable antibacterial and osteogenesis effect. Overall, our study provided a promising strategy for the utilization of piezocatalytic nanomaterials in efficient antibacterial and bone regeneration.

The association of a disability-targeted cash transfer programme with disability status and health-care access: a quasi-experimental study using a nationwide cohort of 4·3 million Chinese adults living with severe disabilities.

BACKGROUND: Cash transfer is a crucial policy tool to address inequality. The objective of this study was to investigate the association between China's disability-targeted cash transfer programme and disability status, as well as equitable access to rehabilitation and medical services. METHODS: For this quasi-experimental study, we drew data from the nationwide administrative cohort of individuals with disabilities between Jan 1, 2015, and Dec 31, 2019. Individuals were enrolled in the cohort if they were aged 18 years or older, had severe disabilities as defined by the Chinese Government, and had available cash transfer information for at least 4 consecutive years, without having started receiving cash transfer benefits at the time of enrolment. We used a quasi-experimental design with propensity score matching to estimate the effects of cash transfers on disability status, access to rehabilitation services, and access to medical treatment. The primary outcomes were development of new disability and reduction of existing disabilities. Secondary outcomes were use of rehabilitation services, financial barriers as a major obstacle to accessing rehabilitation services, use of medical services by individuals who had an illness in the previous 2 weeks, and financial barriers as a major obstacle to accessing medical services. FINDINGS: From an initial pool of 51 356 125 individuals with disabilities registered in the administrative system, 2 686 024 individuals were eligible for analysis, of whom 2 165 335 (80·6%) were cash transfer beneficiaries and 520 689 (19·4%) non-beneficiaries. After propensity score matching, the cohort included 4 330 122 adults with severe disabilities. Cash transfer beneficiaries had significantly lower odds of developing new disabilities over time than non-beneficiaries (odds ratio [OR] 0·90, 95% CI 0·86-0·94; p<0·0001) and higher odds of having a reduced number of disabilities over time (1·17, 1·10-1·25; p<0·0001). Compared with non-beneficiaries, cash transfer beneficiaries were more likely to use rehabilitation services (2·12, 2·11-2·13; p<0·0001) and medical services (1·74, 1·69-1·78; p<0·0001), and less likely to report financial hardship to access rehabilitation services (0·53, 0·52-0·54; p<0·0001) and medical services (0·88, 0·84-0·93; p<0·0001) at the study endpoint. INTERPRETATION: The receipt of cash transfers was associated with improved disability status and increased access to disability-related services. The findings suggest that cash transfers could be a potential method for promoting universal health coverage among individuals living with disabilities. FUNDING: China National Natural Science Foundation.

Augmenting Intracellular Cargo Delivery of Extracellular Vesicles in Hypoxic Tissues through Inhibiting Hypoxia-Induced Endocytic Recycling.

As mesenchymal stem-cell-derived small extracellular vesicles (MSC-sEVs) have been widely applied in treatment of degenerative diseases, it is essential to improve their cargo delivery efficiency in specific microenvironments of lesions. However, the interaction between the microenvironment of recipient cells and MSC-sEVs remains poorly understood. Herein, we find that the cargo delivery efficiency of MSC-sEVs was significantly reduced under hypoxia in inflammaging nucleus pulposus cells due to activated endocytic recycling of MSC-sEVs. Hypoxia-inducible factor-1 (HIF-1)-induced upregulated RCP (also known as RAB11FIP1) is shown to promote the Rab11a-dependent recycling of internalized MSC-sEVs under hypoxia via enhancing the interaction between Rab11a and MSC-sEV. Based on this finding, si-RCP is loaded into MSC-sEVs using electroporation to overcome the hypoxic microenvironment of intervertebral disks. The engineered MSC-sEVs significantly inhibit the endocytic recycling process and exhibit higher delivery efficiency under hypoxia. In a rat model of intervertebral disk degeneration (IDD), the si-RCP-loaded MSC-sEVs successfully treat IDD with improved regenerative capacity compared with natural MSC-sEV. Collectively, the findings illustrate the intracellular traffic mechanism of MSC-sEVs under hypoxia and demonstrate that the therapeutic capacity of MSC-sEVs can be improved via inhibiting endocytic recycling. This modifying strategy may further facilitate the application of extracellular vesicles in hypoxic tissues.

Treatment of posttraumatic equinus deformity and concomitant soft tissue defects of the heel.

BACKGROUND: To evaluate the operative method and clinical outcome for the treatment of posttraumatic equinus deformity and concomitant soft tissue defect of the heel. METHODS: Between June 2006 and May 2010, seven cases of posttraumatic equinus deformity and concomitant unstable scar or ulcer of the heels were treated by using a hinged Ilizarov apparatus and reversed sural fasciocutaneous island flap transfer. Achilles tendon lengthening was also done in all patients. The average duration of follow-up was 21 months. The sizes of sural flaps were from 7 cm × 6 cm to 10 cm × 9 cm. Two weeks after the flap transfer, distraction of the Ilizarov fixator was initiated to gradually correct the equinus position of the foot. RESULTS: Results were evaluated by using the following criteria: (1) the degree of active dorsiflexion of the ankle, (2) the total active range of motion of the ankle, and (3) walking ability and flap durability. For active dorsiflexion of the ankle, the results were good in three patients and fair in four patients. For range of active motion of the ankle, the results were good in five patients and fair in two patients. For walking ability and flap durability, the results were good in six patients and fair in one patient. CONCLUSION: This study showed that posttraumatic equinus deformity accompanied by soft tissue defect of the heel can be treated effectively with Achilles tendon lengthening, reversed sural fasciocutaneous island flap transfer, and a hinged Ilizarov technique.