Augmented Extraction Efficiency of a Hot D Exciton in MoS2 via Intervalley Scattering.

Prolonging hot carrier cooling, a crucial factor in optoelectronic applications, including hot carrier photovoltaics, presents a significant challenge. High-energy band-nesting excitons within parallel bands offer a promising and underexplored avenue for addressing this issue. Here, we exploit an exceptional D exciton cooling prolongation of 2 to 3 orders of magnitude compared to sub-picosecond in typical transition metal dichalcogenides (TMDs) owing to the complex Coulomb environment and the sequential and mismatch-valley relaxation. Simultaneously, the intervalley scattering upconversion of band-edge excitons with the slow D exciton formation in the metastable Γ valley/hill also reduces the cooling rate. We successfully extract D and C excitons as hot carriers through integrating with various thicknesses of TiOx, achieving the highest efficiency of 98% and 85% at a Ti thickness of 2 nm. Our findings highlight the potential of band-nesting excitons for extending hot carrier cooling time, paving the way for advancements in hot carrier-based optoelectronic devices.

Synergetic Dual-Additive Electrolyte Enables Highly Stable Performance in Sodium Metal Batteries.

Sodium (Na)-metal batteries (SMBs) are considered one of the most promising candidates for the large-scale energy storage market owing to their high theoretical capacity (1,166 mAh g-1) and the abundance of Na raw material. However, the limited stability of electrolytes still hindered the application of SMBs. Herein, sulfolane (Sul) and vinylene carbonate (VC) are identified as effective dual additives that can largely stabilize propylene carbonate (PC)-based electrolytes, prevent dendrite growth, and extend the cycle life of SMBs. The cycling stability of the Na/NaNi0.68Mn0.22Co0.1O2 (NaNMC) cell with this dual-additive electrolyte is remarkably enhanced, with a capacity retention of 94% and a Coulombic efficiency (CE) of 99.9% over 600 cycles at a 5 C (750 mA g-1) rate. The superior cycling performance of the cells can be attributed to the homogenous, dense, and thin hybrid solid electrolyte interphase consisting of F- and S-containing species on the surface of both the Na metal anode and the NaNMC cathode by adding dual additives. Such unique interphases can effectively facilitate Na-ion transport kinetics and avoid electrolyte depletion during repeated cycling at a very high rate of 5 C. This electrolyte design is believed to result in further improvements in the performance of SMBs.

Design, synthesis, biological evaluation and molecular docking of alkoxyaurones as potent pancreatic lipase inhibitors.

Aurones are a minor subgroup of flavonoids. Unlike other subgroups such as chalcones, flavones, and isoflavones, aurones have not been extensively explored as pancreatic lipase inhibitors. In this work, we studied the pancreatic lipase inhibitory potency of synthetic aurone derivatives. Thirty-six compounds belonging to four series (4,6-dihydroxyaurone, 6-hydroxyaurone, 4,6-dialkoxyaurone, and 6-alkoxyaurone) were designed and synthesized. Their in vitro inhibitory activities were determined by spectrophotometric assay in comparison with quercetin and orlistat. Alkoxyaurone derivatives with long-chain (6-10 carbons) alkoxy substituents showed greater potency. Of them, 4,6-dialkoxyaurone 8 displayed the highest activity against pancreatic lipase (IC50 of 1.945 ± 0.520 µM) relative to quercetin (IC50 of 86.98 ± 3.859 µM) and orlistat (IC50 of 0.0334 ± 0.0015 µM). Fluorescence quenching measurement confirmed the affinity of alkoxyaurone derivatives to pancreatic lipase. Kinetic study showed that 8 inhibited lipase through a competitive mechanism (Ki of 1.288 ± 0.282 µM). Molecular docking results clarified the role of long-chain substituents on ring A in interacting with the hydrophobic pockets and pushing the inhibitor molecule closer to the catalytic triad. The findings in this study may contribute to the development of better pancreatic lipase inhibitors with aurone structure.

Focal point technology: Controlling treatment depth and pattern of skin injury by a novel highly focused laser.

BACKGROUND: Selective photothermolysis has limitations in efficacy and safety for dermal targets. We describe a novel concept using scanned focused laser microbeams for precise control of dermal depth and pattern of injury, using a 1550 nm laser that generates an array of conical thermal zones while minimizing injury to the epidermis. OBJECTIVE: To characterize the conical thermal zones in vivo and determine safe starting parameters to transition to a second phase to explore potential clinical indications. METHODS: A focused toroidal (ring) laser beam was delivered through a cold sapphire window, sparing epidermal injury in a central zone. Pulse energy, lesion depth, density, and energy delivery were titrated in ex vivo human skin and subsequently on the backs of 21 human subjects. RESULTS: Histology showed microscale patterns of thermal injury, which varied predictably with laser parameters. Time-course healing through histology and skin surface imaging demonstrated the ability of the device to deliver high energies without sequelae. LIMITATIONS: Clinical data are currently being collected to further explore the safety and efficacy of the device. CONCLUSION: The 1550 nm laser with focal point technology enables precise control of lesion depth while simultaneously sparing a large portion of the epidermis, lowering the risk of adverse effects.

Implementing living-donor pediatric liver transplantation in Southern Vietnam: 15-year results and perspectives.

BACKGROUND: ND2 in Ho Chi Minh City is currently the only public center that performs PLT in Southern Vietnam. In 2005, the first PLT was successfully performed, with support from Belgian experts. This study reviews the implementation of PLT at our center and evaluates the results and challenges. METHODS: Implementation of PLT at ND2 required medico-surgical team building and extensive improvement of hospital facilities. Records of 13 transplant recipients from 2005 to 2020 were studied retrospectively. Short- and long-term complications, as well as the survival rates, were reported. RESULTS: The mean follow-up time was 8.3 ± 5.7 years. Surgical complications included one case of hepatic artery thrombosis that was successfully repaired, one case of colon perforation resulting in death from sepsis, and two cases of bile leak that were drained surgically. PTLD was observed in five patients, of whom three died. There were no cases of retransplantation. The 1-year, 5-year, and 10-year patient survival rates were 84.6%, 69.2%, and 69.2%, respectively. There were no cases of complication or death among the donors. CONCLUSION: Living-donor PLT was developed at ND2 for providing a life-saving treatment to children with end-stage liver disease. Early surgical complication rate was low, and the patient survival rate was satisfactory at 1 year. Long-term survival decreased considerably due to PTLD. Future challenges include surgical autonomy and improvement of long-term medical follow-up with a particular emphasis on prevention and management of Epstein-Barr virus-related disease.

A novel small molecule, AS1, reverses the negative hedonic valence of noxious stimuli.

BACKGROUND: Pain is the primary reason people seek medical care, with chronic pain affecting ~ 20% of people in the USA. However, many existing analgesics are ineffective in treating chronic pain, while others (e.g., opioids) have undesirable side effects. Here, we describe the screening of a small molecule library using a thermal place aversion assay in larval zebrafish to identify compounds that alter aversion to noxious thermal stimuli and could thus serve as potential analgesics. RESULTS: From our behavioral screen, we discovered a small molecule, Analgesic Screen 1 (AS1), which surprisingly elicited attraction to noxious painful heat. When we further explored the effects of this compound using other behavioral place preference assays, we found that AS1 was similarly able to reverse the negative hedonic valence of other painful (chemical) and non-painful (dark) aversive stimuli without being inherently rewarding. Interestingly, targeting molecular pathways canonically associated with analgesia did not replicate the effects of AS1. A neuronal imaging assay revealed that clusters of dopaminergic neurons, as well as forebrain regions located in the teleost equivalent of the basal ganglia, were highly upregulated in the specific context of AS1 and aversive heat. Through a combination of behavioral assays and pharmacological manipulation of dopamine circuitry, we determined that AS1 acts via D1 dopamine receptor pathways to elicit this attraction to noxious stimuli. CONCLUSIONS: Together, our results suggest that AS1 relieves an aversion-imposed "brake" on dopamine release, and that this unique mechanism may provide valuable insight into the development of new valence-targeting analgesic drugs, as well as medications for other valence-related neurological conditions, such as anxiety and post-traumatic stress disorder (PTSD).

Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

Annona glabra L. Seeds: An Agricultural Waste Biosorbent for the Eco-Friendly Removal of Methylene Blue.

The seeds of Annona glabra L., an invasive plant in Vietnam, were first employed as a new biosorbent for the adsorption of methylene blue (MB) from aqueous media. The characterizations of the material using FT-IR, SEM, nitrogen adsorption-desorption analysis, and point of zero charge reveals that it possesses a rough and irregular surface, various polar functional groups, and pHpzc of 5.5. Certain adsorption conditions including adsorbent dose, solution pH, contact time, and initial concentration of MB were found to affect adsorption efficiency. The kinetic data are well fitted with pseudo-second-order model with the adsorption rate of 0.002 g mg-1 min-1 and initial rate of 4.46 mg g-1 min-1. For the adsorption isotherm, three nonlinear models were used to analyze the experiment data, including Langmuir, Freundlich, and Temkin. The results indicate that the Langmuir model best describes the adsorption of Annona glabra L. seeds powder (AGSP) with a maximum adsorption capacity of 98.0 mg g-1. The investigation underpins the adsorption mechanism, whereby the electrostatic attraction between positively charged MB and negatively charged surface of AGSP is expected to be the predominant mechanism, together with hydrogen bonding and pi-pi interaction. These results make AGSP an interesting biosorbent concerning its environmental friendliness, cost-effectiveness, and relatively high dye adsorption capacity.

Utilization of dragon fruit (Hylocereus undatus) peel-derived biochar for the adsorptive removal of tetracycline from aqueous solution.

The peel of Hylocereus undatus was employed in the preparation of biochar and firstly applied for tetracycline removal from aqueous solution. Based on different characterization techniques, the material was found to possess a variety of surface functional groups on a porous structure and a pH point of zero charge (pHpzc) of 9.3. Adsorption of tetracycline (TC) was conducted under varying conditions, revealing significant effects of carbonization temperature, solution pH, adsorbent dose, ionic strength, contact time and initial concentration of TC on the biochar adsorption capacity. Kinetic data on TC adsorption were best described using the Elovich kinetic model, with an initial adsorption rate of 167.3 mg g-1 min-1. Isotherm data on adsorption of the desired biochar showed the best fit with the Temkin isotherm model, followed by the Langmuir model, displaying maximum adsorption capacity at 12.4 mg g-1. The electrostatic interactions between the charged biochar surfaces and certain fractions of TC were proposed as the major mechanism, together with H-bonding, pore-filling effect and π-π interaction. This study demonstrates great potential of H. undatus peel as a starting material to prepare an effective and reusable adsorbent in the removal of TC.

Literature is available on a large number of plant-based biochar adsorbents for the removal of antibiotics. However, to the best of our knowledge, no report has been published on applying biochar derived from Hylocereus undatus peel for antibiotics removal. This type of fruit peel is available in massive amounts in Vietnam and is considered as an agricultural solid waste. Therefore, to fill the gap in the literature and to converse this leftover waste into a value-added byproduct, we chose this study to prepare H. undatus peel-derived biochar for the elimination of TC in an aqueous solution.

Investigating the impacts of climate change on hydroclimatic extremes in the Tar-Pamlico River basin, North Carolina.

Evaluating the forthcoming impacts of climate change is important for formulating efficient and flexible approaches to water resource management. General Circulation Models (GCMs) are primary tools that enable scientists to study both past and potential future climate changes, as well as their impacts on policies and actions. In this work, we quantify the future projected impacts of hydroclimatic extremes on the coastal, risk-prone Tar-Pamlico River basin in North Carolina using GCMs from the Sixth International Coupled Model Intercomparison Project (CMIP6). These models incorporate projected future societal development scenarios (Shared Socioeconomic Pathways, SSPs) as defined in the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report (AR6). Specifically, we have utilized historical residential expansion data, the Soil and Water Assessment Tool Plus (SWAT+), the Standardized Precipitation Index (SPI), and the Interquartile Range (IQR) method for analyzing extremes from 2024 to 2100. Our findings include: (1) a trend toward wetter conditions is identified with an increase in flood events toward 2100; (2) projected increases in the severity of flood peaks are found, quantified by a rise of 21% compared to the 2000-2020 period; (3) downstream regions are forecast to experience severe droughts up to 2044; and (4) low-lying and coastal regions are found as particularly susceptible to higher flood peaks and more frequent drought events between 2045 and 2100. This work provides valuable insights into the anticipated shifts in natural disaster patterns and supports decision-makers and authorities in promoting adaptive strategies and sustainable policies to address challenges posed by future climate changes in the Tar-Pamlico region and throughout the state of North Carolina, United States.

Characterization of Syzygium cumini (L.) Skeels (Jamun Seed) Particulate Fillers for Their Potential Use in Polymer Composites.

Syzgium cumini (L.) Skeels powder (S. cumini powder), also known as Jamun, is well-known for its various medical and health benefits. It is especially recognized for its antidiabetic and antioxidant properties. Thus, S. cumini powder is used in various industries, such as the food and cosmetic industries. In this work, the fruit of S. cumini was utilized; its seeds were extracted, dried, and ground into powder. The ground powders were subjected to various techniques such as physicochemical tests, Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), particle size analysis, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and antioxidant analysis. From the physicochemical tests, it was revealed that the jamun seed filler contained cellulose (43.28%), hemicellulose (19.88%), lignin (23.28%), pectin (12.58%), and wax (0.98%). The FTIR analysis supported these results. For instance, a peak at 2889 cm-1 was observed and associated with CH stretching, typically found in methyl and methylene groups, characteristic of cellulose and hemicellulose structures. The XRD results demonstrated that the crystallinity index of the jamun seed filler was 42.63%. The particle analysis indicated that the mean (average) particle size was 25.34 µm. This observation was ensured with SEM results. The EDX spectrum results showed the elemental composition of the fillers. Regarding thermal degradation, the jamun seed filler had the ability to withstand temperatures of up to 316.5 °C. Furthermore, endothermic and exothermic peaks were observed at 305 °C and 400 °C, respectively. Furthermore, the antioxidant property of the powder displayed a peak scavenging activity of 91.4%. This comprehensive study not only underscores the viability of S. cumini powder as a sustainable and effective particulate filler in polymer composites but also demonstrates its potential to enhance the mechanical properties of composites, thereby offering significant implications for the development of eco-friendly materials in various industrial applications.

Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

Sequential targeting of PARP with carboplatin inhibits primary tumour growth and distant metastasis in triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) develop early recurrence. While PARP inhibitors (PARPi) have demonstrated potential in BRCA1/2-mutant (BRCAMUT) TNBC, durable responses will likely be achieved if PARPi are used in combination. It is plausible that sequential administration of a potent PARPi like talazoparib in combination with carboplatin can enhance primary tumour and metastasis inhibition in BRCAMUT and BRCA1/2 wild-type (BRCAWT) TNBCs, and decrease toxicity. METHODS: We evaluated the impact of the concurrent combination of talazoparib and carboplatin on cell survival in 13 TNBC cell lines. We compared the concurrent and sequential combination upon fork replication, migration and invasion. We also used three orthotopic xenograft models to evaluate primary tumour growth, distant metastasis, and toxicity. RESULTS: Concurrent talazoparib and carboplatin was synergistic in 92.3% of TNBC cell lines, independent of BRCA1/2-mutation status. The sequential combination decreased fork speed in normal cells, but not in TNBC cells. The talazoparib-first sequential combination resulted in a strong reduction in migration (70.4%, P < 0.0001), invasion (56.9%, P < 0.0001), lung micrometastasis (56.4%, P < 0.0001), and less toxicity in a BRCAWT model. CONCLUSION: The sequential combination of talazoparib and carboplatin is an effective approach to inhibit micrometastatic disease, providing rationale for the use of this combination in early TNBC patients.

Correction: Site-specific analysis of N-glycans from different sheep prion strains.

[This corrects the article DOI: 10.1371/journal.ppat.1009232.].

Site-specific analysis of N-glycans from different sheep prion strains.

Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans. During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration. In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains. Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP). Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking. Here we report the characterization and comparison of N-glycans from two different sheep prion strains. PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin. By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed. A total of 100 structures were detected on both glycosylation sites. The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported. The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.

Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma.

BACKGROUND: Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. METHODS: Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. RESULTS: Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. CONCLUSIONS: Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

Detection of preceding sleep apnea using ECG spectrogram during CPAP titration night: A novel machine-learning and bag-of-features framework.

Obstructive sleep apnea (OSA) has a heavy health-related burden on patients and the healthcare system. Continuous positive airway pressure (CPAP) is effective in treating OSA, but adherence to it is often inadequate. A promising solution is to detect sleep apnea events in advance, and to adjust the pressure accordingly, which could improve the long-term use of CPAP treatment. The use of CPAP titration data may reflect a similar response of patients to therapy at home. Our study aimed to develop a machine-learning algorithm using retrospective electrocardiogram (ECG) data and CPAP titration to forecast sleep apnea events before they happen. We employed a support vector machine (SVM), k-nearest neighbour (KNN), decision tree (DT), and linear discriminative analysis (LDA) to detect sleep apnea events 30-90 s in advance. Preprocessed 30 s segments were time-frequency transformed to spectrograms using continuous wavelet transform, followed by feature generation using the bag-of-features technique. Specific frequency bands of 0.5-50 Hz, 0.8-10 Hz, and 8-50 Hz were also extracted to detect the most detected band. Our results indicated that SVM outperformed KNN, LDA, and DT across frequency bands and leading time segments. The 8-50 Hz frequency band gave the best accuracy of 98.2%, and a F1-score of 0.93. Segments 60 s before sleep events seemed to exhibit better performance than other pre-OSA segments. Our findings demonstrate the feasibility of detecting sleep apnea events in advance using only a single-lead ECG signal at CPAP titration, making our proposed framework a novel and promising approach to managing obstructive sleep apnea at home.

Discovery of novel flavonoid derivatives as potential dual inhibitors against α-glucosidase and α-amylase: virtual screening, synthesis, and biological evaluation.

Diabetes mellitus is one of the top ten causes of death worldwide, accounting for 6.7 million deaths in 2021, and is one of the most rapidly growing global health emergencies of this century. Although several classes of therapeutic drugs have been invented and applied in clinical practice, diabetes continues to pose a serious and growing threat to public health and places a tremendous burden on those affected and their families. The strategy of reducing carbohydrate digestibility by inhibiting the activities of α-glucosidase and α-amylase is regarded as a promising preventative treatment for type 2 diabetes. In this study, we investigated the dual inhibitory effect against two polysaccharide hydrolytic enzymes of flavonoid derivatives from an in-house chemical database. By combining molecular docking and structure-activity relationship analysis, twelve compounds with docking energies less than or equal to - 8.0 kcal mol-1 and containing required structural features for dual inhibition of the two enzymes were identified and subjected to chemical synthesis and in vitro evaluation. The obtained results showed that five compounds exhibited dual inhibitory effects on the target enzymes with better IC50 values than the approved positive control acarbose. Molecular dynamics simulations were performed to elucidate the binding of these flavonoids to the enzymes. The predicted pharmacokinetic and toxicological properties suggest that these compounds are viable for further development as type 2 diabetes drugs.

Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation.

IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future.

Socio-economic and agricultural factors associated with stunting of under 5-year children: findings from surveys in mountains, dry zone and delta regions of rural Myanmar (2016-2017).

OBJECTIVE: The study's objective was to investigate multiple underlying social, economic and agricultural determinants of stunting among under-five children in three distinct ecological areas in rural Myanmar. DESIGN: Repeated cross-sectional surveys in three states of Myanmar. SETTING: Rural households in Chin (mountainous), Magway (plains) and Ayeyarwady (delta). PARTICIPANTS: From two purposively selected adjacent townships in each state, we randomly selected twenty villages and, in each village, thirty households with under-five children. Households in the first survey in 2016 were revisited in late 2017 to capture seasonal variations. RESULTS: Stunting increased from 40·4 % to 42·0 %, with the highest stunting prevalence in Chin state (62·4%). Univariate Poisson regression showed factors contributing to child stunting varied across the regions. Adjusted Poisson regression models showed that child's age and short maternal stature (aRR = 1·14 for Chin, aRR = 1·89 for Magway and aRR = 1·86 for Ayeyarwady) were consistently associated with child stunting across three areas. For Chin, village-level indicators such as crop consumption (aRR = 1·18), crop diversity (aRR = 0·82) and land ownership (aRR = 0·89) were significantly associated with stunting. In Magway, the number of household members (aRR = 1·92), wealth status (aRR = 0·46), food security status (aRR = 1·14), land ownership (aRR = 0·85) and in Ayeyarwady, women's decision-making (aRR = 0·67) and indicators related to hygiene (aRR = 1·13) and sanitation (aRR = 1·45) were associated with stunting. CONCLUSIONS: Area-specific factors were associated with stunting. Maternal short stature and child age were consistent determinants of stunting. A multi-sectoral local approach, including improvements in transport, is needed to address the intergenerational malnutrition problem.