Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

[Mechanism of acupotomy on chondrocyte ferroptosis in rabbits with knee osteoarthritis based on HSPA5/GPX4 signaling pathway].

OBJECTIVE: To observe the effect of acupotomy on heat shock protein A family member 5 (HSPA5)/glutathione peroxidase 4 (GPX4) signaling pathway in the chondrocytes of the rabbits with knee osteoarthritis (KOA) and explore the mechanism of acupotomy on chondrocyte ferroptosis in KOA. METHODS: Twenty-seven New Zealand rabbits were randomly divided into a normal group, a model group and an acupotomy group, with 9 rabbits in each group. The left hind limb was fixed by the modified Videman method for 6 weeks to establish KOA model. After modeling, acupotomy was given in the acupotomy group, once a week and for consecutive 3 weeks. Using Lequesne MG score, the local symptoms, physical signs and functions of knee joint were evaluated. With HE staining and saffrane-solid green staining adopted, the morphology of chondrocytes and cartilage tissue was observed. Under transmission electron microscope, the mitochondrial structure of chondrocytes was observed. The iron content of cartilage tissue was detected by iron ion kit. The mitochondrial membrane potential (Δψm) and the reactive oxygen species (ROS) level in cartilage tissue were determined by flow cytometry, and the mitochondrial damage rate was calculated. The mRNA expression of HSPA5, GPX4, type Ⅱ collagen α1 chain (COL2A1), matrix metalloproteinases (MMP) 3 and MMP13 was detected by the real-time quantitative PCR; and the protein expression of HSPA5, GPX4, type Ⅱ collagen (COL-Ⅱ), MMP3 and MMP13 was detected by Western blot. The mean flourscence intensity of HSPA5 and GPX4 in cartilage tissue was determined by immunofluorescence. RESULTS: Before intervention, compared with the normal group, the Lequesne MG scores were increased in the model group and the acupotomy group (P<0.01). After intervention, the Lequesne MG score in the acupotomy group was decreased when compared with that in the model group. In comparison with that in the normal group, the number of chondrocytes was reduced and the cells were disarranged; the layers of cartilage structure were unclear, the tide lines disordered and blurred; the mitochondria were wrinkled and the mitochondrial crista decreased or even disappeared in the model group. Compared with the model group, the number of chondrocytes was increased, the layers of cartilage structure were clear, the tide lines recovered, the number of mitochondria elevated, with normal structure and more crista in the acupotomy group. The iron content of cartilage tissue was increased (P<0.01), the Δψm of chondrocytes was declined, the mitochondrial damage rate was increased (P<0.01), the average fluorescence intensity of ROS was increased (P<0.01); the mRNA and corresponding protein expression of HSPA5, GPX4 and COL2A1 was decreased (P<0.01), the mRNA and protein expression of MMP3 and MMP13 was increased (P<0.01) and the average fluorescence intensity of HSPA5, GPX4 was decreased (P<0.01) in the model group when compared with those in the normal group. Compared with the model group, the iron content in cartilage tissue was reduced (P<0.01), the Δψm of chondrocytes was increased, the mitochondrial damage rate was decreased (P<0.01), and the average fluorescence intensity of ROS was decreased (P<0.01); the mRNA and corresponding protein expression of HSPA5, GPX4 and COL2A1 was higher (P<0.01), and the mRNA and protein expression of MMP3 and MMP13 was lower, and the average fluorescence intensity of HSPA5, GPX4 was increased (P<0.01) in the acupotomy group. CONCLUSION: Acupotomy can alleviate cartilage injury of KOA rabbits, and its mechanism may be related to the regulation of HSPA5/GPX4 signaling pathway to maintain iron homeostasis in articular cartilage, thus inhibiting chondrocyte ferroptosis and relieving extracellular matrix degradation.

Design, Synthesis and Biological Evaluation of Novel Phenyl-Substituted Naphthoic Acid Ethyl Ester Derivatives as Strigolactone Receptor Inhibitor.

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.

Gestational supplementation of Bifidobacterium, Lactobacillus, and Streptococcus thermophilus attenuates hepatic steatosis in offspring mice through promoting fatty acid ß-oxidation.

Currently, Bifidobacterium, Lactobacillus, and Streptococcus thermophilus (BLS) are widely recognized as the crucially beneficial bacteria in the gut. Many preclinical and clinical studies have shown their protective effects against non-alcoholic fatty liver disease (NAFLD). However, whether gestational BLS supplementation could alleviate NAFLD in the offspring is still unknown. Kunming mice were given a high-fat diet (HFD) for 4 weeks before mating. They received BLS supplementation by gavage during pregnancy. After weaning, offspring mice were fed with a regular diet up to 5 weeks old. Gestational BLS supplementation significantly increased the abundance of Actinobacteriota, Bifidobacterium, and Faecalibaculum in the gut of dams exposed to HFD. In offspring mice exposed to maternal HFD, maternal BLS intake significantly decreased the ratio of Firmicutes to Bacteroidetes as well as the relative abundance of Prevotella and Streptococcus, but increased the relative abundance of Parabacteroides. In offspring mice, maternal BLS supplementation significantly decreased the hepatic triglyceride content and mitigated hepatic steatosis. Furthermore, maternal BLS supplementation increased the glutathione content and reduced malondialdehyde content in the liver. In addition, mRNA and protein expression levels of key rate-limiting enzymes in mitochondrial ß-oxidation (CPT1α, PPARα, and PGC1α) in the livers of offspring mice were significantly increased after gestational BLS supplementation. Thus, gestational BLS supplementation may ameliorate maternal HFD-induced steatosis and oxidative stress in the livers of offspring mice by modulating fatty acid ß-oxidation.

Self-Catalyzed, Visible-Light-Induced Selective C3-H Aroylation of Quinoxalin-2(1H)-ones with Arylaldehydes by Air as an Oxidant.

A self-catalyzed, visible-light-induced, directly selective C3-H aroylation of quinoxalin-2(1H)-ones via energy transfer and hydrogen atom transfer (HAT) catalysis has been developed. The method is highly atom-economical, eco-friendly, and easy to handle. Notably, the reaction proceeded efficiently with ambient air as the sole oxidant at room temperature.

Lipid accumulation product is a valid predictor of hepatic steatosis and nonalcoholic fatty liver disease.

Aims: To evaluate and compare lipid accumulation product (LAP) with alanine aminotransferase (ALT), aspartate aminotransferase (AST), visceral adiposity index (VAI) and triglyceride-glucose index (TyG) as biomarkers for hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Methods: LAP, ALT, AST, VAI and TyG were measured in 52 biopsy-proven NAFLD patients and 21 control subjects. Additionally, LAP was also measured in 448 ultrasound-proven NAFLD patients and 1009 control subjects. Results: LAP was positively associated with hepatic steatosis and inflammation in biopsy-proven NAFLD. The risk of NAFLD was positively related to LAP and TyG, but LAP showed a better area under the receiver operating characteristic curve for hepatic steatosis and NAFLD. LAP also performed well in recognizing ultrasound-proven NAFLD. Conclusion: LAP is an ideal biomarker of hepatic steatosis and NAFLD.

A capture-based method of prenatal cell-free DNA screening for autosomal recessive non-syndromic hearing loss.

OBJECTIVE: This study aimed to develop and validate a prenatal cell-free DNA (cfDNA) screening method that uses capture-based enrichment to genotype fetal autosomal recessive disorders. This method was applied in pregnancies at high risk of autosomal recessive non-syndromic hearing loss (ARNSHL) to assess its accuracy and effectiveness. METHODS: This assay measured the allele counts in both white blood cell DNA and cfDNA from the blood samples of pregnant women using a capture-based next-generation sequencing method. It then applied a binomial model to infer the fetal genotypes with the maximum likelihood. Ninety-four pregnant couples that were carriers of variants of ARNSHL in GJB2 or SLC26A4 were enrolled. The fetal genotypes deduced using this screening method were compared with the results of genetic diagnosis using amniocentesis. RESULTS: Of the 94 couples, 65 carried more than one variant, resulting in 170 single-nucleotide polymorphism (SNP) loci to be inferred in the fetuses. Of the 170 fetal SNP genotypes, 150 (88.2%) had high confidence calls and 139 (92.7%) of these matched the genotypes obtained by amniocentesis result. Out of the remaining 20 (11.8%) cases with low-confidence calls, only 14 (70.0%) were concordant with genetic diagnosis using amniocentesis. The concordance rate was 100% for sites where the maternal genotype was wild-type homozygous. The discordance was site-biased, with each locus showing a consistent direction of discordance. Genetic diagnosis identified a total of 19 wild-type homozygotes, 46 heterozygotes, 19 compound heterozygotes, and 10 pathogenic homozygotes. This screening method correctly genotyped 81.9% (77/94) of fetuses and demonstrated a sensitivity of 89.7% and a specificity of 89.2% for correctly identifying ARNSHL. CONCLUSION: This capture-based method of prenatal screening by cfDNA demonstrated strong potential for fetal genotyping of autosomal recessive disorders.

Volatilomics-Based Discovery of Key Volatiles Affecting Flavor Quality in Tomato.

Volatile accumulation during tomato ripening greatly affects the fruit flavor. In this study, four accessions from each of the three tomato subgroups (BIG, S. lycopersicum, CER, S. lycopersicumvar. Cerasiforme, and PIM, S. pimpinellifolium) were subjected to a sensory evaluation. The CER subgroup had the highest fruit-flavor score. Using a Headspace solid-phase microextraction/gas chromatography-mass spectrometer (HP-SPME/GC-MS), a volatile database containing 94 volatiles was created. Pentanal accumulated in green fruits and 1-pentanol in red fruits. 1-Octen-3-ol was discovered to underlie the bitterness of green tomatoes, and it was most abundant in PIM green fruits. Phenylethyl alcohol affected the acidity and sweetness of red tomatoes, and it was most abundant in CER red fruits. Branched-chain volatiles were most abundant in PIM and BIG red fruits, while apocarotenoids were most abundant in CER red fruits. These findings suggest that domestication and improvement have influenced volatile content, and apocarotenoids and branched-chain volatiles synergistically mediated aromatic flavors in red fruits. This study provides a metabolic basis for analyses of the molecular mechanisms of fruit-flavor formation.

Novel copy number variations and phenotypes of infantile epileptic spasms syndrome.

We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% (12/74) were 1p36 deletion, and 20.3% (15/74) were 15q11-q13 duplication. The age of seizure onset ranged from 17 days to 24 months. Seizure types included epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, and hemangioma. 29.7% of patients were seizure-free for more than 12 months, and 70.3% still had seizures after trying 2 or more anti-seizure medications. In conclusion, CNVs is a prominent etiology of IESS. 1p36 deletion and 15q duplication occurred most frequently. CNV detection should be performed in patients with IESS of unknown causes, especially in children with craniofacial anomalies and microcephaly.

Detecting and quantifying Veillonella by real-time quantitative PCR and droplet digital PCR.

Veillonella spp. are Gram-negative opportunistic pathogens present in the respiratory, digestive, and reproductive tracts of mammals. An abnormal increase in Veillonella relative abundance in the body is closely associated with periodontitis, inflammatory bowel disease, urinary tract infections, and many other diseases. We designed a pair of primers and a probe based on the 16S rRNA gene sequences of Veillonella and conducted real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR) to quantify the abundance of Veillonella in fecal samples. These two methods were tested for specificity and sensitivity using simulated clinical samples. The sensitivity of qPCR was 100 copies/µL, allowing for the accurate detection of a wide range of Veillonella concentrations from 103 to 108 CFU/mL. The sensitivity of ddPCR was 11.3 copies/µL, only allowing for the accurate detection of Veillonella concentrations from 101 to 104 CFU/mL because of the limited number of droplets generated by ddPCR. ddPCR is therefore more suitable for the detection of low-abundance Veillonella samples. To characterize the validity of the assay system, clinical samples from children with inflammatory bowel disease were collected and analyzed, and the results were verified using isolation methods. We conclude that molecular assays targeting the 16S rRNA gene provides an important tool for the rapid diagnosis of chronic and infectious diseases caused by Veillonella and also supports the isolation and identification of Veillonella for research purposes. KEY POINTS: • With suitable primer sets, the qPCR has a wider detection range than ddPCR. • ddPCR is suitable for the detection of low-abundance samples. • Methods successfully guided the isolation of Veillonella in clinical sample.

Prophylactic vitamin C supplementation regulates DNA demethylation to protect against cisplatin-induced acute kidney injury in mice.

Cisplatin-induced acute kidney injury (AKI) restricts the use of cisplatin as a first-line chemotherapeutic agent. Our previous study showed that prophylactic vitamin C supplementation may act as an epigenetic modulator in alleviating cisplatin-induced AKI in mice. However, the targets of vitamin C and the mechanisms underlying the epigenetics changes remain largely unknown. Herein, whole-genome bisulfite sequencing and bulk RNA sequencing were performed on the kidney tissues of mice treated with cisplatin with prophylactic vitamin C supplementation (treatment mice) or phosphate-buffered saline (control mice) at 24 h after cisplatin treatment. Ascorbyl phosphate magnesium (APM), an oxidation-resistant vitamin C derivative, was found that led to global hypomethylation in the kidney tissue and regulated different functional genes in the promoter region and gene body region. Integrated evidence suggested that APM enhanced renal ion transport and metabolism, and reduced apoptosis and inflammation in the kidney tissues. Strikingly, Mapk15, Slc22a6, Cxcl5, and Cd44 were the potential targets of APM that conferred protection against cisplatin-induced AKI. Moreover, APM was found to be difficult to rescue cell proliferation and apoptosis caused by cisplatin in the Slc22a6 knockdown cell line. These results elucidate the mechanism by which vitamin C as an epigenetic regulator to protects against cisplatin-induced AKI and provides a new perspective and evidence support for controlling the disease process through regulating DNA methylation.

Microstructure engineering in sulfuretted coal tar pitch by varying the Cross-Link state for enhanced sodium storage.

Sulfur (S) is an efficient dopant to enhance the sodium storage of carbon, yet the conventional in-situ/post treatments cause unstable S configuration or lower S content, and hence unsatisfied electrochemical performance. Herein, we investigate sulfurization at various cross-link state of coal tar pitch (CTP) (pristine, coke, and carbonized states), and the microstructure of the products (SCTP). Experimental and calculational results reveal that introducing S in the coke state of CTP is essential for achieving abundant and stable C-Sx-C bonds between carbon layers. Moreover, this innovative strategy not only achieves a high S content, but also avoids the liquid carbonization, resulting in a hierarchically porous structure with a small particle size. As a result, the SCTP delivers a sodium storage capacity of 318 mA h g-1 at 0.1 A g-1 after 200th cycle, and the capacity maintains 207 mA h g-1 with capacity retention of 99 % after 1000th cycle at 2.0 A g-1, in half-cells. Moreover, the sample shows a considerable discharge capacity of 328 mA h g-1anode at 0.05 A g-1 in full-cells. Consequently, this approach offers a novel pathway for large-scale production of thermoplastic-derived carbons in battery industry.

Deep Image Matting With Sparse User Interactions.

Image matting is a fundamental and challenging problem in computer vision and graphics. Most existing matting methods leverage a user-supplied trimap as an auxiliary input to produce good alpha matte. However, obtaining high-quality trimap itself is arduous. Recently, some hint-free methods have emerged, however, the matting quality is still far behind the trimap-based methods. The main reason is that, some hints for removing semantic ambiguity and improving matting quality are essential. Apparently, there is a trade-off between interaction cost and matting quality. To balance performance and user-friendliness, we propose an improved deep image matting framework which is trimap-free and only needs sparse user click or scribble interaction to minimize the needed auxiliary constraints while still allowing interactivity. Moreover, we introduce uncertainty estimation that predicts which parts need polishing and conduct uncertainty-guided refinement. To trade off runtime against refinement quality, users can also choose different refinement modes. Experimental results show that our method performs better than existing trimap-free methods and comparably to state-of-the-art trimap-based methods with minimal user effort. Finally, we demonstrate the extensibility of our framework to video human matting without any structure modification, by adding optical flow-based sparse hint propagation and temporal consistency regularization imposed on the single frame.

Co-delivery of drugs by adhesive transdermal patches equipped with dissolving microneedles for the treatment of rheumatoid arthritis.

In this study, a dosage form consisting of dissolving (D) microneedles (M) and an adhesive (A) transdermal patch (P; DMAP) was designed and pre-clinically evaluated for the treatment of rheumatoid arthritis (RA). The tip of the dissolving microneedles (DMNs) was loaded with the macromolecular drug melittin (Mel@DMNs), this to treat joint inflammation and bone damage, while the adhesive transdermal patches contained the low molecular weight drug diclofenac sodium (DS; DS@AP) for pain relief. Mel@DMNs and DS@AP were ingeniously connected through an isolation layer for compounding Mel-DS@DMAP for the simultaneous delivery of the drugs. In vitro and in vivo experiments showed that DS@AP did not affect the mechanical properties and dissolution process of Mel@DMNs while the pores formed by the microneedles promoted the skin penetration of DS. Treatment of rats suffering from RA with Mel-DS@DMAP reduced paw swelling and damage of the synovium, joint and cartilage, suggesting that the 'patch-microneedle' dosage form might be promising for the treatment and management of RA.

Nitrogen and Sulfur Co-doped Carbon Quantum Dots for Detecting Fe3+, Ascorbic Acid and Alkaline Phosphatase Activities.

A method utilizing nitrogen-doped and sulfur-doped carbon quantum dots (N, S-CQDs) as fluorescent probes for the rapid detection of Fe3+, L-ascorbic acid (AA), and alkaline phosphatase (ALP) was presented. The fluorescence intensity of N, S-CQDs nanoprobes can be rapidly and efficiently quenched by Fe3+ and based on the fluorescence "turn off-on" characteristic of N, S-CQDs nanoprobes, the fluorescence signals of the N, S-CQDs/Fe3+can be recovered after the addition of AA. By coupling a fluorescent nanoprobe to an enzyme and L-ascorbic acid-2-phosphate (AA2P), a green, simple, rapid and effective fluorescent analytical method for the determination of ALP was developed. The prepared N, S-CQDs showed high sensitivity and selectivity to Fe3+, AA and ALP with the detection limit of 0.42 µM, 12.7 nM and 0.017 U·L-1 and their optimal concentration ranges were10-600 µM, 10-200 µM, 0.18-54 U·L-1, respectively. The fluorescence quantum yield of N, S-CQDs (0.2 mg·mL-1) at 393 nm excitation wavelength was 4.41%. Additionally, the fluorescent nanoprobes have been employed to successfully measure ALP in serum samples. It is expected that the established method may offer a new approach for biomolecular detection in clinical diagnosis and pharmaceutical analysis.

Identification of a Novel Oxidative Stress- and Anoikis-Related Prognostic Signature and Its Immune Landscape Analysis in Non-Small Cell Lung Cancer.

The objective of this study was to identify a kind of prognostic signature based on oxidative stress- and anoikis-related genes (OARGs) for predicting the prognosis and immune landscape of NSCLC. Initially, We identified 47 differentially expressed OARGs that primarily regulate oxidative stress and epithelial cell infiltration through the PI3K-Akt pathway. Subsequently, 10 OARGs related to prognosis determined two potential clusters. A cluster was associated with a shorter survival level, lower immune infiltration, higher stemness index and tumor mutation burden. Next, The best risk score model constructed by prognostic OARGs was the Random Survival Forest model, and it included SLC2A1, LDHA and PLAU. The high-risk group was associated with cluster A and poor prognosis, with a higher tumor mutation burden, stemness index and proportion of M0-type macrophages, and a lower immune checkpoint expression level, immune function score and IPS score. The calibration curve and decision-making curve showed that the risk score combined with clinical pathological characteristics could be used to construct a nomogram for guiding the clinical treatment strategies. Finally, We found that all three hub genes were highly expressed in tumor tissues, and LDHA expression was mainly regulated by has-miR-338-3p, has-miR-330-5p and has-miR-34c-5p. Altogether, We constructed an OARG-related prognostic signature to reveal potential relationships between the signature and clinical characteristics, TME, stemness, tumor mutational burden, drug sensitivity and immune landscape in NSCLC patients.

Molecular Identification and Genetic Characterization of Public Health Threatening Ticks - Chongming Island, China, 2021-2022.

What is already known about this topic?: Although ticks and tick-borne diseases are prevalent throughout China, there remains a knowledge gap regarding their biology and potential risk of distribution to human and animal populations on Chongming Island. The island, being China's third largest and a crucial component in the ecological preservation of the Yangtze Delta region, has yet to be comprehensively studied in this context. What is added by this report?: In this study, employing molecular methodologies, a significant prevalence of Haemaphysalis (H.) longicornis and H. flava ticks - widely recognized for their high pathogenicity - is reported from Chongming Island. Additionally, the identification of two previously unreported species on the island, namely, H. doenitzi and H. japonica, expands our understanding of both the range and evolution of tick species. What are the implications for public health practice?: The populations of humans and animals in nearly all 18 towns on Chongming Island are potentially at risk for transmission of tick-borne infectious agents. As a result, there is a pressing necessity for public health alerts, proactive tick surveillance, and effective screening of suspected clinical cases of tick-borne diseases within the Chongming population.

Understanding the China-Tanzania Malaria Control Project: lessons learned from a multi-stakeholder qualitative study.

Background: Tanzania is among the countries with the highest malaria cases and deaths worldwide, where vulnerable populations have been severely affected due to poverty and weakness in health system and infrastructure. The China-Tanzania Malaria Control Project (the Project) was a two-phase global health intervention project implemented between 2015 and 2021 that aimed to transfer project-designated intervention experience in malaria elimination to the Tanzanian health system. This study aims to identify the barriers and facilitators encountered during the Project and to improve our understanding of the emerging phenomenon of South-South global health collaboration. Methods: We conducted thematic analysis of qualitative data collected from a purposive sample of 14 participants from multiple stakeholders including project management office, project implementation agency, funding partners and external evaluators of the Project. A conceptual framework was developed to construct the interviews guides. The interviews were transcribed verbatim, crossover checked, translated into English, and analyzed with NVivo 12.0. We conducted the open coding followed by the axial coding based on the Grounded Theory to generate themes and subthemes, and identified key influencing factors that aided or hindered the malaria control in Tanzania. Results: The findings suggested that malaria control strategies should largely be tailored due to varied socioeconomic contexts. The perceived enablers in practice include project-designated intervention experiences and technologies, professional and self-learning capabilities of the implementation team, sustainable financial assistance, and support from the international partners. The barriers include the shortage of global health talents, existing gaps to meet international standards, defects in internal communication mechanisms, inadequacy of intergovernmental dialogue, and limitations in logistical arrangements. A checklist and policy implications for China's future engagement in malaria control in resource-limited settings have been proposed. Conclusions: The initiative of Health Silk Road has generated strong global interest in promoting development assistance in health. In the hope of generalizing the evidence-based interventions to high malaria-endemic countries in Africa, the need for China to carefully face the challenges of funding gaps and the lack of support from recipient governments remains ongoing. It is recommended that China should form an institutionalized scheme and sustainable funding pool to ensure the steady progress of development assistance in health.

The role of integration host factor in biofilm and virulence of high-alcohol-producing Klebsiella pneumoniae.

Klebsiella pneumoniae is a well-known human nosocomial pathogen with an arsenal of virulence factors, including capsular polysaccharides (CPS), fimbriae, flagella, and lipopolysaccharides (LPS). Our previous study found that alcohol acted as an essential virulence factor for high-alcohol-producing K. pneumoniae (HiAlc Kpn). Integration host factor (IHF) is a nucleoid-associated protein that functions as a global virulence regulator in Escherichia coli. However, the regulatory role of IHF in K. pneumoniae remains unknown. In the present study, we found that deletion of ihfA or ihfB resulted in a slight defect in bacterial growth, a severe absence of biofilm formation and cytotoxicity, and a significant reduction in alcohol production. RNA sequencing differential gene expression analysis showed that compared with the wild-type control, the expression of many virulence factor genes was downregulated in ΔihfA and ΔihfB strains, such as those related to CPS (rcsA, galF, wzi, and iscR), LPS (rfbABCD), type I and type III fimbriae (fim and mrk operon), cellulose (bcs operon), iron transporter (feoABC, fhuA, fhuF, tonB, exbB, and exbD), quorum sensing (lsr operon and sdiA), type II secretion system (T2SS) and type VI secretion system (T6SS) (tssG, hcp, and gspE). Of these virulence factors, CPS, LPS, fimbriae, and cellulose are involved in biofilm formation. In addition, IHF could affect the alcohol production by regulating genes related to glucose intake (ptsG), pyruvate formate-lyase, alcohol dehydrogenase, and the tricarboxylic acid (TCA) cycle. Our data provided new insights into the importance of IHF in regulating the virulence of HiAlc Kpn. IMPORTANCE Klebsiella pneumoniae is a well-known human nosocomial pathogen that causes various infectious diseases, including urinary tract infections, hospital-acquired pneumonia, bacteremia, and liver abscesses. Our previous studies demonstrated that HiAlc Kpn mediated the development of nonalcoholic fatty liver disease by producing excess endogenous alcohol in vivo. However, the regulators regulating the expression of genes related to metabolism, biofilm formation, and virulence of HiAlc Kpn remain unclear. In this study, the regulator IHF was found to positively regulate biofilm formation and many virulence factors including CPS, LPS, type I and type III fimbriae, cellulose, iron transporter, AI-2 quorum sensing, T2SS, and T6SS in HiAlc Kpn. Furthermore, IHF positively regulated alcohol production in HiAlc Kpn. Our results suggested that IHF could be a potential drug target for treating various infectious diseases caused by K. pneumoniae. Hence, the regulation of different virulence factors by IHF in K. pneumoniae requires further investigation.