Amine Switchable Hydrophilic Solvent Vortex-Assisted Homogeneous Liquid-Liquid Microextraction and GC-MS for the Enrichment and Determination of 2, 6-DIPA Additive in Biodegradable Film.

2, 6-diisopropylaniline (2, 6-DIPA) is a crucial non-intentionally organic additive that allows the assessment of the production processes, formulation qualities, and performance variations in biodegradable mulching film. Moreover, its release into the environment may have certain effects on human health. Hence, this study developed simultaneous heating hydrolysis-extraction and amine switchable hydrophilic solvent vortex-assisted homogeneous liquid-liquid microextraction for the gas chromatography-mass spectrometry analysis of the 2, 6-DIPA additive and its corresponding isocyanates in poly(butylene adipate-co-terephthalate) (PBAT) biodegradable agricultural mulching films. The heating hydrolysis-extraction conditions and factors influencing the efficiency of homogeneous liquid-liquid microextraction, such as the type and volume of amine, homogeneous-phase and phase separation transition pH, and extraction time were investigated and optimized. The optimum heating hydrolysis-extraction conditions were found to be a H2SO4 concentration of 2.5 M, heating temperature of 87.8 °C, and hydrolysis-extraction time of 3.0 h. As a switchable hydrophilic solvent, dipropylamine does not require a dispersant. Vortex assistance is helpful to speed up the extraction. Under the optimum experimental conditions, this method exhibits a better linearity (0.0144~7.200 µg mL-1 with R = 0.9986), low limit of detection and quantification (0.0033 µg g-1 and 0.0103 µg g-1), high extraction recovery (92.5~105.4%), desirable intra- and inter-day precision (relative standard deviation less than 4.1% and 4.7%), and high enrichment factor (90.9). Finally, this method was successfully applied to detect the content of the additive 2, 6-DIPA in PBAT biodegradable agricultural mulching films, thus facilitating production process monitoring or safety assessments.

SKP2-mediated ubiquitination and degradation of KLF11 promotes osteoarthritis via modulation of JMJD3/NOTCH1 pathway.

Osteoarthritis (OA) is the main cause of cartilage damage and disability. This study explored the biological function of S-phase kinase-associated protein 2 (SKP2) and Kruppel-like factor 11 (KLF11) in OA progression and its underlying mechanisms. C28/I2 chondrocytes were stimulated with IL-1ß to mimic OA in vitro. We found that SKP2, Jumonji domain-containing protein D3 (JMJD3), and Notch receptor 1 (NOTCH1) were upregulated, while KLF11 was downregulated in IL-1ß-stimulated chondrocytes. SKP2/JMJD3 silencing or KLF11 overexpression repressed apoptosis and extracellular matrix (ECM) degradation in chondrocytes. Mechanistically, SKP2 triggered the ubiquitination and degradation of KLF11 to transcriptionally activate JMJD3, which resulted in activation of NOTCH1 through inhibiting H3K27me3. What's more, the in vivo study found that KLF11 overexpression delayed OA development in rats via restraining apoptosis and maintaining the balance of ECM metabolism. Taken together, ubiquitination and degradation of KLF11 regulated by SKP2 contributed to OA progression by activation of JMJD3/NOTCH1 pathway. Our findings provide promising therapeutic targets for OA.

Developing hydrogels for gene therapy and tissue engineering.

Hydrogels are a class of highly absorbent and easily modified polymer materials suitable for use as slow-release carriers for drugs. Gene therapy is highly specific and can overcome the limitations of traditional tissue engineering techniques and has significant advantages in tissue repair. However, therapeutic genes are often affected by cellular barriers and enzyme sensitivity, and carrier loading of therapeutic genes is essential. Therapeutic gene hydrogels can well overcome these difficulties. Moreover, gene-therapeutic hydrogels have made considerable progress. This review summarizes the recent research on carrier gene hydrogels for the treatment of tissue damage through a summary of the most current research frontiers. We initially introduce the classification of hydrogels and their cross-linking methods, followed by a detailed overview of the types and modifications of therapeutic genes, a detailed discussion on the loading of therapeutic genes in hydrogels and their characterization features, a summary of the design of hydrogels for therapeutic gene release, and an overview of their applications in tissue engineering. Finally, we provide comments and look forward to the shortcomings and future directions of hydrogels for gene therapy. We hope that this article will provide researchers in related fields with more comprehensive and systematic strategies for tissue engineering repair and further promote the development of the field of hydrogels for gene therapy.

Mating harassment may boost the effectiveness of the sterile insect technique for Aedes mosquitoes.

The sterile insect technique is based on the overflooding of a target population with released sterile males inducing sterility in the wild female population. It has proven to be effective against several insect pest species of agricultural and veterinary importance and is under development for Aedes mosquitoes. Here, we show that the release of sterile males at high sterile male to wild female ratios may also impact the target female population through mating harassment. Under laboratory conditions, male to female ratios above 50 to 1 reduce the longevity of female Aedes mosquitoes by reducing their feeding success. Under controlled conditions, blood uptake of females from an artificial host or from a mouse and biting rates on humans are also reduced. Finally, in a field trial conducted in a 1.17 ha area in China, the female biting rate is reduced by 80%, concurrent to a reduction of female mosquito density of 40% due to the swarming of males around humans attempting to mate with the female mosquitoes. This suggests that the sterile insect technique does not only suppress mosquito vector populations through the induction of sterility, but may also reduce disease transmission due to increased female mortality and lower host contact.

Metformin eliminates lymphedema in mice by alleviating inflammation and fibrosis: implications for human therapy.

BACKGROUND: Secondary lymphedema is a chronic, disabling disease impacting over 50% of patients with cancer and lacking effective pharmacological treatment even for early- to mid-disease stages. Metformin reportedly exerts anti-inflammatory and anti-fibrotic effects and is safe, with minimal side effects; We investigated the role of metformin in lymphedema mouse models and examined underlying molecular mechanisms. METHODS: Male C57BL/6 mice (6-8-week-old; n=15/group) received metformin (300 mg/kg/day) by gavage on day 3 after lymphedema surgery; saline and sham groups were administered the same volume of saline. Hindlimb circumference and tail volume were monitored every two days. On day 28, samples were collected for histological assessment, western blotting, and reverse transcription-quantitative PCR analysis of inflammation, fibrosis, and AMPK expression. AMPK activity was assayed in patients with secondary lymphedema (ISL II) and controls following strict inclusion criteria. RESULTS: Compared with the saline group, the metformin group exhibited hindlimb circumference and tail volume reduced by 469.70% and 305.18%, respectively. on day 28. Dermal thickness was reduced by 38.27% and 72.57% in the hindlimbs and tail, respectively. Metformin decreased CD4+ T cell infiltration by 19.73% and expression levels of interleukin (IL)-4, IL-13, IL-17, and transforming growth factor-ß1. Additionally, it lowered collagen I deposition by 33.18%. Compared with the saline group, the number of lymphatic vessels increased by 229.96% in the metformin group. Both the saline group mice and patients with lymphedema showed reduced AMPK activity, while metformin increased p-AMPK expression by 106.12%. CONCLUSION: Metformin alleviated inflammation and fibrosis and increased lymphangiogenesis in lymphedema mouse models by activating AMPK signaling.

HSF1 Increases EOGT-Mediated Glycosylation of Notch1 to Promote IL-1ß-Induced Inflammatory Injury of Chondrocytes.

OBJECTIVE: Osteoarthritis (OA) is the most common arthritic disease in humans. Nevertheless, the pathogenic mechanism of OA remains unclear. This study aimed to explore that heat-shock transcription factor 1 (HSF1) facilitated interleukin-1 beta (IL-1ß) chondrocyte injury by increasing Notch1 O-linked N-acetylglucosamine (O-GlcNAc) modification level. DESIGN: Human chondrocytes were incubated with 5 ng/ml interleukin-1 beta (IL-1ß) for 24 h to establish OA cell model. The messenger RNA (mRNA) or protein expressions were assessed using reverse transcription-quantitative polymerase chain reaction, western blot, or immunofluorescence. Chondrocyte viability was examined by Cell Counting Kit-8 assay. Enzyme-linked immunosorbent assay was employed to detect the secretion levels of interleukin-6 (IL-6) and interleukin-8 (IL-8). Immunoprecipitation was adopted to detect Notch1 O-GlcNAc modification level. The interaction between HSF1 and epidermal growth factor-like (EGF) domain-specific O-GlcNAc transferase (EOGT) promoter was analyzed by dual-luciferase reporter gene and chromatin immunoprecipitation assays. RESULTS: Herein, our results demonstrated that HSF1, EOGT, Notch1, and Notch1 intracellular domain (NICD1) expressions in chondrocytes were markedly increased by IL-1ß stimulation. EOGT elevated Notch1 expression in IL-1ß-treated chondrocytes by increasing Notch1 O-GlcNAc modification level. EOGT silencing reduced IL-1ß-induced chondrocyte inflammatory injury. In addition, HSF1 knockdown relieved IL-1ß-induced chondrocyte inflammatory injury. Molecular interaction experiment proved that HSF1 transcriptionally activated EOGT expression in IL-1ß-treated chondrocytes. CONCLUSIONS: HSF1 promoted IL-1ß-induced inflammatory injury in chondrocytes by increasing EOGT-mediated glycosylation of Notch1.

The METTL3/miR-196a Axis Predicts Poor Prognosis in Non-small Cell Lung Cancer.

Background: METTL3 accelerates m6A modification to influence cancer progression including non-small cell lung cancer (NSCLC). To illustrate the role and underlying mechanism of METTL3 mediated miR-196a upregulation in NSCLC. Method: The global level of m6A modification was detected by qPCR, western blot and immumohistochemical staining. The TCGA, GEPIA, CPTAC and TIMER databases were used to explore the expression change of METTL3, miR-196a and GAS7 in NSCLC patients. Kaplan-Meier analysis was performed to analyze the prognostic value of miR-196a. NSCLC cells overexpressed or knockdown miR-196a were constructed and used for CCK8, colony formation assay, western blot and immunofluorescence in vitro. The effect of miR-196a on tumor growth was investigated in vivo. Result: We found that METTL3 mediated miR-196a were notably enhancive in NSCLC tissues and in NSCLC cells, which is markedly positively related with the serious TNM stage, the large tumor size, the distant metastasis, and the poor prognosis in patients of NSCLC. Further investigation showed that up-regulated miR-196a promoted cell viability and cell autophagy, while down-regulation of miR-196a revealed opposite results in H1299 and A549 cells. In terms of mechanism, we found that miR-196a interacted with GAS7. In addition, GAS7 expression in NSCLC patients may be positively related with the infiltration of immune cell subsets in tumor microenvironment (TME). Conclusion: The axis of METTL3-miR-196a-GAS7 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for NSCLC patients.

Response of soil N2O production pathways to biochar amendment and its isotope discrimination methods.

Reducing nitrous oxide (N2O) emission from farmland is crucial for alleviating global warming since agriculture is an important contributor of atmospheric N2O. Returning biochar to agricultural fields is an important measure to mitigate soil N2O emissions. Accurately quantifying the effect of biochar on the process of N2O production and its driving factors is critical for achieving N2O emission mitigation. Recently, stable isotope techniques such as isotope labeling, natural abundance, and site preference (SP) value, have been widely used to distinguish N2O production pathways. However, the different isotope methods have certain limitations in distinguishing N2O production in biochar-amended soils where it is difficult to identify the relative contribution of individual pathways for N2O production. This paper systematically reviews the pathways of soil N2O production (nitrification, nitrifier denitrification, bacterial denitrification, fungal denitrification, coupled nitrification-denitrification, dissimilatory nitrate reduction to ammonium and abiotic processes) and their response mechanism to the addition of biochar, as well as the development history and advantages of isotopes in differentiating N2O production pathways in biochar-amended soils. Moreover, the limitations of current research methods and future research directions are proposed. These results will help resolve how biochar affects different processes that lead to soil N2O generation and provide a scientific basis for sustainable agricultural carbon sequestration and the fulfilment of carbon neutrality goals.

Hemostatic effect and safety evaluation of oxidized regenerated cellulose in total knee arthroplasty- a randomized controlledtrial.

BACKGROUND: Oxidized regenerated cellulose (ORC) is a type of biodegradable hemostatic material, which has been widely used in the field of surgery. However, its hemostatic effect in patients undergoing total knee arthroplasty (TKA) is uncertain. Accordingly, this study investigated the effectiveness and safety of ORC in patients receiving TKA. METHODS: Seventy patients undergoing unilateral TKA were randomized into blank control group and ORC (2 pieces of ORC placed in the joint cavity) groups. Then, the two groups were compared for primary (perioperative blood loss [total blood loss, intraoperative blood loss, and hidden blood loss] and hemoglobin drop values) and secondary (coagulation indicators, inflammatory indicators,operation time, and complication rates) outcomes. RESULTS: The total blood loss in the ORC group was 902.32 ± 307.82 mL, which was statistically significantly lower than that in the control group (1052.25 ± 308.44 mL) (P < 0.05). Postoperative hidden blood loss was also statistically markedly lower in the ORC group (801.61 ± 298.80 mL) than in the control group (949.96 ± 297.59 mL) (P < 0.05). There was no significant difference between the two groups in terms of coagulation indicators, inflammatory indicators, operation time, and complication rates. CONCLUSION: In conclusion, our prospective RCT study proved that regenerated oxidized cellulose can be used safely in vivo and can effectively reduce postoperative blood loss in patients, which is a potential method for preventing blood loss after TKA. TRIAL REGISTRATION: This prospective RCT was reviewed and approved by the Ethics Committee of Honghui Hospital of Xi'an Jiaotong University (No: 202,211,007) and was designed and conducted according to the rules of the Declaration of Helsinki. Written informed consent was obtained from patients or their legal guardians.

Metabolome and Transcriptome Association Analysis Reveals the Link Between Pigmentation and Nutrition Utilization in the Juveniles of Sea Cucumber Holothuria leucospilota.

The sea cucumber Holothuria leucospilota is an economically and ecologically important tropical species. Following development into juveniles, H. leucospilota undergoes a color change from white to black, involving a pigmentation process for over a period of several months. In this study, a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Next-Generation sequencing (NGS) were employed to investigate the changes in metabolomic and transcriptomic profiles during pigmentation in H. leucospilota juveniles. The metabolomic analysis identified a total of 341 metabolites, of which 52 were found to be differentially regulated (P < 0.05 and VIP > 1), with 27 being upregulated in white individuals and 25 in black individuals. Additionally, 632 differentially expressed genes (DEGs) were identified, with 380 genes upregulated in white samples and 252 genes upregulated in black samples. Interestingly, the melanin content and tyrosinase transcript levels did not display significant differences between the two groups. Metabolomic data suggested the involvement of the linoleic acid metabolic pathway in pigmentation. Transcriptomic analysis, coupled with realtime PCR validation, revealed a decrease in the transcript levels of digestive enzymes like α-amylase, maltase-glucoamylase, and trehalase after the juveniles changed to black. Furthermore, the mRNA expressions of major yolk proteins showed a decline, indicating a shift in the accumulation of protein nutrient sources. Overall, our findings suggest that during the pigmentation process in H. leucospilota, no significant changes were observed in the classical melanin pathway, while notable alterations were observed in their nutritional status. This study provides valuable insights into the regulatory mechanisms of pigmentation in marine organisms.

Applications of Environmental DNA (eDNA) in Monitoring the Endangered Status and Evaluating the Stock Enhancement Effect of Tropical Sea Cucumber Holothuria Scabra.

The tropical sea cucumber Holothuria scabra is naturally found in the Indo-West Pacific. However, due to their commercial value, natural H. scabra populations have declined significantly in recent years, resulting in its status as an endangered species. Surveys of H. scabra resource pose a challenge due to its specific characteristics, such as sand-burrowing behavior. To overcome this problem, our study established a convenient and feasible method for assessing H. scabra resources using environmental DNA (eDNA) monitoring technology. First, H. scabra-specific TaqMan primers and probe were designed based on its cox1 gene, followed by the development of an eDNA monitoring method for H. scabra in two separate sea areas (Xuwen and Daya Bay). The method was subsequently employed to investigate the distribution of H. scabra and assess the effects of aquaculture stock enhancement through juvenile releasing in the Weizhou Island sea area. The H. scabra eDNA monitoring approach was found to be more appropriate and credible than traditional methods, and a positive impact of stocking on H. scabra populations was observed. In summary, this is the first report to quantify eDNA concentration in a Holothuroidea species, and it provides a convenient and accurate method for surveying H. scabra resources. This study introduces novel concepts for eDNA-based detection of endangered marine benthic animals and monitoring their population distribution and abundance.

Effects of enzymatic modification on the stability of cashew-based milk.

The green and low-carbon awareness drives the consumption demand for "clean-label" plant-based milk, which is limited by its physicochemical stability. Herein, the effects of enzymatic hydrolysis on the stability of cashew-based milk (CM) are explored in detail. Our results showed that a maximum protein solubility of 41.36 ± 2.14% was achieved under bromelain treatment of CM either for 60 min or with the addition of 600 U g-1. Under these hydrolysis conditions, CM showed smaller particle size, larger zeta potential, and more uniform size distribution in comparison with the control. Similar behavior was also observed in the apparent viscosity and macroscopic stability, demonstrating the fortification of moderate hydrolysis on the physical stability of CM. Interestingly, bromelain hydrolysis could favor improving the oxidative stability of CM, for which the peroxide value and thiobarbituric acid reactive substances were decreased by 90% and 60%, respectively, after 14 days of storage in comparison with the control. The correlation analysis confirmed that the physical and oxidative stability was highly associated with protein solubility and secondary structures like α-helix. Therefore, our findings could provide scientific support for developing plant-based milk with fortified physicochemical stability.

[Advances in treatment of lymphedema with supraclavicular vascularized lymph node transfer].

Objective: To review the research progress of supraclavicular vascularized lymph node transfer (VLNT). Methods: The research literature related to supraclavicular VLNT at home and abroad in recent years was extensively reviewed, and the anatomy of supraclavicular lymph nodes, clinical applications, and complications of supraclavicular VLNT were summarized. Results: The supraclavicular lymph nodes are anatomically constant, located in the posterior cervical triangle zone, and the blood supply comes mainly from the transverse cervical artery. There are individual differences in the number of supraclavicular lymph nodes, and preoperative ultrasonography is helpful to clarify the number of lymph nodes. Clinical studies have shown that supraclavicular VLNT can relieve limb swelling, reduce the incidence of infection, and improve quality of life in patients with lymphedema. And the effectiveness of supraclavicular VLNT can be improved by combined with lymphovenous anastomosis, resection procedures, and liposuction. Conclusion: There are a large number of supraclavicular lymph nodes, with abundant blood supply. It has been proven to be effective for any period of lymphedema, and the combined treatment is more effective. The more clinical studies are needed to clarify the effectiveness of supraclavicular VLNT alone or in combination, as well as the surgical approach and timing of the combined treatment.

Progressively Hybrid Transformer for Multi-Modal Vehicle Re-Identification.

Multi-modal (i.e., visible, near-infrared, and thermal-infrared) vehicle re-identification has good potential to search vehicles of interest in low illumination. However, due to the fact that different modalities have varying imaging characteristics, a proper multi-modal complementary information fusion is crucial to multi-modal vehicle re-identification. For that, this paper proposes a progressively hybrid transformer (PHT). The PHT method consists of two aspects: random hybrid augmentation (RHA) and a feature hybrid mechanism (FHM). Regarding RHA, an image random cropper and a local region hybrider are designed. The image random cropper simultaneously crops multi-modal images of random positions, random numbers, random sizes, and random aspect ratios to generate local regions. The local region hybrider fuses the cropped regions to let regions of each modal bring local structural characteristics of all modalities, mitigating modal differences at the beginning of feature learning. Regarding the FHM, a modal-specific controller and a modal information embedding are designed to effectively fuse multi-modal information at the feature level. Experimental results show the proposed method wins the state-of-the-art method by a larger 2.7% mAP on RGBNT100 and a larger 6.6% mAP on RGBN300, demonstrating that the proposed method can learn multi-modal complementary information effectively.

Salecan confers anti-inflammatory effects in liver injury via regulating gut microbiota and its metabolites.

Salecan, a natural ß-glucan and one of the novel food ingredients approved in China, has been shown a variety of positive health effects, yet the mechanism of liver injury remains poorly understood. In addition, ß-glucan could induce the shifts in gut microbiota, however, whether modulation of gut microbiota by ß-glucan is associated with their positive health effects remain elusive. Here, the anti-inflammatory effects and the underlying mechanism of Salecan supplementation in CCl4-induced liver injury were investigated. After 8 weeks of treatment, we observed that Salecan alleviated liver injury by regulating inflammatory response and M2 macrophage polarization. In addition, Salecan treatment modulated the composition of gut microbiota and antibiotic cocktail treatment indicated that the hepatoprotective effect of Salecan was dependent on the gut microbiota. Fecal microbiota transplantation was used to further verify the mechanism, and we confirmed that microbial colonization partially alleviated liver injury. Besides, microbiota-derived metabolites of Salecan also contributed to the hepatoprotective and anti-inflammatory effect of Salecan against liver injury. These findings supported that Salecan intervention attenuated liver injury by regulating gut microbiota and its metabolites.

Integrative Application of Transcriptomics and Metabolomics Provides Insights into Unsynchronized Growth in Sea Cucumber (Stichopus monotuberculatus).

Ever-increasing consumer demand for sea cucumbers mainly leads to huge damage to wild sea cucumber resources, including Stichopus monotuberculatus, which in turn exerts negative impacts on marine environments due to the lack of ecological functions performed by sea cucumbers. Aquaculture of sea cucumbers is an effective way to meet consumer demand and restore their resources. Unsynchronous growth is a prominent problem in the aquaculture of sea cucumbers which has concealed unelucidated molecular mechanisms until now. In this study, we carried out an integrative analysis of transcriptomics and metabolomics on fast-growing (SMF) and slow-growing (SMS) groups of S. monotuberculatus cultured in the same environmental conditions. The results revealed that a total of 2054 significantly differentially expressed genes (DEGs) were identified, which are mainly involved in fat digestion and absorption, histidine metabolism, arachidonic acid metabolism, and glutathione metabolism. 368 differential metabolites (DMs) were screened out between the SMF group and the SMS group; these metabolites are mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, pyrimidine metabolism, arachidonic acid metabolism, and other metabolic pathways. The integrative analysis of transcriptomics and metabolomics of S. monotuberculatus suggested that the SMF group had a higher capacity for lipid metabolism and protein synthesis, and had a more frequent occurrence of apoptosis events, which are likely to be related to coping with environmental stresses. The results of this study provide potential values for the aquaculture of sea cucumbers which may promote their resource enhancement.

Salecan ameliorates liver injury by regulating gut microbiota and its metabolites.

Salecan, a natural ß-glucan consisting of seven residues linked by ß-(1→3)/α-(1→3) glycosidic bonds, is one of the novel food ingredients approved in China. ß-Glucan has a variety of health-improving effects, yet its mechanism against liver injury remains poorly understood. ß-Glucan can induce shifts in the gut microbiota and show health benefits; however, whether modulation of the gut microbiota by ß-glucan is associated with its benefits remains unclear. Here, the hepatoprotective effect and potential mechanism of salecan supplementation using a model of CCl4-induced liver injury were investigated. After 8 weeks of treatment, salecan alleviated liver injury by regulating oxidative stress and activating the Nrf2 signaling pathway. In addition, salecan treatment modulated the composition of the gut microbiota, and the antibiotic cocktail treatment indicated that the hepatoprotective effect of salecan was dependent on the gut microbiota. Fecal microbiota transplantation was used to further verify this mechanism, and we confirmed that microbial colonization partially alleviated liver injury. Besides, microbiota-derived metabolites of salecan also contributed to the hepatoprotective effect of salecan against liver injury and inhibited oxidative stress. These findings supported that salecan intervention attenuated liver injury by regulating the gut microbiota and its metabolites.

A cross-sectional study to assess the epidemiological situation and associated risk factors of dengue fever; knowledge, attitudes, and practices about dengue prevention in Khyber Pakhtunkhwa Province, Pakistan.

Background: Dengue fever has been responsible for around 12 countrywide large outbreaks in Pakistan, resulting in 286,262 morbidities and 1,108 deaths. Khyber Pakhtunkhwa (KP) is the most recently impacted province. This study aimed to investigate the molecular, epidemiological, and potential elements that contribute to increasing dengue transmission patterns, and knowledge, attitude, and practice (KAP) toward dengue in KP province. Method: This cross-sectional community-based study was conducted (June-December, 2021) in two phases. Phase I involved the epidemiological (n = 5,242) and molecular analysis of DENV in 500 randomly collected blood samples of the 2021 dengue outbreak in KP. Phase II focused on assessing dengue-KAP levels in healthy communities (n = 14,745, aged >18 years), adopting a cross-sectional clustered multistage sampling in eight districts (dengue-hotspot vs. non-hotspot) of KP. Chi-square tests and logistic regression analysis were applied. Results: Peshawar district had the highest dengue cases (60.0%) associated with the predominant co-circulation of DENV-2 (45.8%) and DENV-3 (50.4%) serotypes. A rise in cases was reported in October (41.8%) followed by September (27.9%) and August (14.4%; p < 0.001). Males (63.7%, p < 0.001) and individuals aged 16-30 years (37.0%, p < 0.001) were highly affected. General workers (18.0%), families with a monthly income of 10,000-20,000 Pak rupees (50.5%), unmarried (71.0%), uneducated (31%), families with higher human density (>10 individuals per household), and those (29.0%) who faced power outages for more than 7/24 h were the most affected. Moreover, co-morbidities like renal failure and bronchial asthma were associated with disease severity. A community survey on KAP revealed that an average of 74, 60, and 43% of the participants demonstrated good knowledge, attitudes, and dengue preventive practices, respectively. Conclusion: Multiple poor socioeconomic elements are influencing dengue fever transmission in the province. Higher KAP levels may explain the low frequency of dengue in non-hotspot districts. Our study emphasizes the need for effective and long-term public health education, strengthened vector surveillance, and expanded laboratory capacity for better diagnosis and management of dengue cases to better predict the burden and seasonality of disease in the country.

TFA-Promoted Intermolecular Friedel-Crafts Alkylation of Arenes with 2,2,2-Trifluoroethylaryl Sulfoxides.

The classical Pummerer rearrangement of 2,2,2-trifluoroethylaryl sulfoxide with trifluoracetic anhydride (TFAA) affords the S,O-acetal efficiently. In the presence of trifluoracetic acid (TFA) as the co-solvent, the S,O-acetal can regenerate reactive thionium intermediate of Pummerer rearrangement. When employing arenes as nucleophiles, this strategy produces corresponding 1-thiyl-2,2,2-trifluoroethyl arenes with excellent yields under metal-free conditions.

Novel approach by natural language processing for COVID-19 knowledge discovery.

BACKGROUND: The impact of COVID-19 on public health has mandated an 'all hands on deck' scientific response. The current clinical study and basic research on COVID-19 are mainly based on existing publications or our knowledge of coronavirus. However, efficiently retrieval of accurate, relevant knowledge on COVID-19 can pose significant challenges for researchers. METHODS: To improve quality in accessing important literature findings, we developed a novel natural language processing (NLP) method to automatically recognize the associations among potential targeted host organ systems, associated clinical manifestations, and pathways. We further validated these associations through clinician experts' evaluations and prioritize candidate drug targets through bioinformatics network analysis. RESULTS: We found that the angiotensin-converting enzyme 2 (ACE2), a receptor that SARS-CoV-2 required for cell entry, is associated with cardiovascular and endocrine organ system and diseases. Furthermore, we found SARS-CoV-2 is associated with some important pathways such as IL-6, TNF-alpha, and IL-1 beta-induced dyslipidemia, which are related to inflammation, lipogenesis, and oxidative stress mechanisms, suggesting potential drug candidates. CONCLUSION: We prioritized the list of therapeutic targets involved in antiviral and immune modulating drugs for experimental validation, rendering it valuable during public health crises marked by stresses on clinical and research capacity. Our automatic intelligence pipeline also contributes to other novel and emerging disease management and treatments in the future.