Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor.

The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol-1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.

Microscopic Cracks Modulate Nucleation and Solid-State Crystallization Tendency of Amorphous Celecoxib.

Drugs have been classified as fast, moderate, and poor crystallizers based on their inherent solid-state crystallization tendency. Differential scanning calorimetry-based heat-cool-heat protocol serves as a valuable tool to define the solid-state crystallization tendency. This classification helps in the development of strategies for stabilizing amorphous drugs. However, microscopic characteristics of the samples were generally overlooked during these experiments. In the present study, we evaluated the influence of microscopic cracks on the crystallization tendency of a poorly water-soluble model drug, celecoxib. Cracks developed in the temperature range of 0-10 °C during the cooling cycle triggered the subsequent crystallization of the amorphous phase. Nanoindentation study suggested minimal differences in mechanical properties between samples, although the cracked sample showed relatively inhomogeneous mechanical properties. Nuclei nourishment experiments suggested crack-assisted nucleation, which was supported by Raman data that revealed subtle changes in intermolecular interactions between cracked and uncracked samples. Celecoxib has been generally classified as class II, i.e., a drug with moderate crystallization tendency. Interestingly, classification of amorphous celecoxib may change depending on the presence or absence of cracks in the amorphous sample. Hence, subtle events such as microscopic cracks should be given due consideration while defining the solid-state crystallization tendency of drugs.

What Is the Likelihood of Union and Frequency of Complications After Parallel Plating and Supplemental Bone Grafting for Resistant Distal Femoral Nonunions?

BACKGROUND: Management of resistant distal femur nonunions is challenging because patients not only have disability from an unhealed fracture, but also often have a shortened femur, stiff knee, deformities, and bone defects to address during revision surgery. Dual plating of the distal femur in such a setting can maintain stability that allows the nonunion to heal while also addressing bone defects and correcting deformities simultaneously. Dual-plating techniques that have been described lack standardization with regard to the size and type of medial-side implants and configuration of the dual-plate construct. QUESTIONS/PURPOSES: (1) What proportion of patients achieve radiologic evidence of union after parallel plating of resistant distal femoral nonunions? (2) What improvements in function are achieved with this approach, as assessed by improvements in femoral length discrepancy, knee flexion, and patient-reported outcome scores? (3) What complications are associated with the technique? METHODS: Between 2017 and 2020, the senior author of this study treated 38 patients with resistant distal femoral nonunions, defined here as nonunions that persisted for more than 12 months since the injury despite a minimum of two previous internal fixation procedures. During the study period, our preferred technique for treating aseptic, resistant distal femoral nonunions was to use dual plates in a parallel configuration augmented with autografts. Of 38 patients, three patients with active signs of infection who underwent resection and reconstruction using bone transport techniques and two patients older than 65 years with deficient distal femur bone stock who underwent endoprosthetic reconstruction were excluded. Of the 33 included patients, 67% (22 of 33) were male. The median age was 40 years (range 20 to 67 years). Nonunion was articular and metaphyseal in 13 patients and metaphyseal only in 20 patients. Our surgical approach was to remove existing implants, perform intraoperative culturing to rule out infection, debride the nonunion, correct the deformity, perform intra-articular and extra-articular lysis of adhesions with quadriceps release, and apply fixation using medial and lateral fixed-angle anatomic locked implants positioned in a parallel configuration. Every attempt to improve length was undertaken, and the defects were filled with autografts. A total of 97% of patients were followed until union occurred (one of 33 was lost to follow-up before union was documented), and 79% (26 of 33) were assessed for functional outcomes at a minimum of 2 years (median 38 months [range 25 to 60 months]) after excluding patients lost to follow-up and those in whom union did not occur after parallel plating. Union was defined as evidence of central trabecular bridging on AP radiographs and posterior cortical bridging on lateral radiographs. These radiologic criteria were defined to overcome difficulties in assessing radiologic healing in patients with lateral and medial plates. With parallel plating, bridging trabecular bone along the posterior cortex on lateral radiographs and the central region on AP radiographs is visualized and can be appreciated and interpreted as evidence of healing in two orthogonal planes. Preoperative and follow-up clinical assessment of knee ROM, the extent of femoral length correction based on calibrated femoral radiographs before and after surgery, and the evaluation of improvement in lower limb function based on the preoperative and follow-up differences in responses to the lower extremity functional scale (LEFS) were studied (the LEFS is scored from 0 to 80, with higher scores representing better function). Complications and secondary surgical procedures to address them were abstracted from a longitudinally maintained trauma database. RESULTS: Sixty-seven percent (22 of 33) of nonunions showed radiologic healing by 24 weeks, and another 24% (eight of 33) healed by 36 weeks. Six percent (two of 33) did not unite, and one patient was lost to follow-up before union was documented. In the 79% (26 of 33) of patients available for final functional outcome assessment, the median femoral shortening had improved from 2.4 cm (range 0 to 4 cm) to 1.1 cm (range 0 to 2.3 cm; p < 0.001), and the median knee ROM had improved from 70° (range 20° to 110°) to 100° (range 50° to 130°; p = 0.002) after surgery. The median LEFS score improved to 63 (range 41 to 78) compared with 22 (range 15 to 33; p < 0.001) before surgery. Serious complications, including major thromboembolic events, iliac graft site infection, knee stiffness (flexion < 60°), and medial plate impingement necessitating removal, were seen in 30% (10 of 33) of patients. Secondary surgical interventions were performed in 24% (eight of 33) of patients to address procedure-related complications. CONCLUSION: Based on our findings, a high likelihood of union and improvements in knee and lower limb function can be expected with parallel plating of resistant distal femur nonunions using anatomic locked plates. However, the increased frequency of complications observed in our study suggests the need for improvements in dual-plating techniques and to explore possible alternative fixation methods through larger multicenter comparative studies. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Tricuspid valve annular tilt for assessment of pre- and post-intervention right ventricular volume in patients undergoing transcatheter pulmonary valve replacement.

INTRODUCTION: Transcatheter pulmonary valve replacement serves as a successful alternative to surgical replacement of a right ventricle to pulmonary artery conduit. Guidelines for recommending transcatheter pulmonary valve replacement depend on MRI right ventricular volumes, which have been correlated to the echocardiographic measure of right ventricular annular tilt. We aim to assess whether right ventricular annular tilt can be a clinically useful alternative tool in the acute and long-term periods after transcatheter pulmonary valve replacement to assess right ventricular health. METHODS: We reviewed 70 patients who underwent transcatheter pulmonary valve replacement at a single institution. Echocardiographic measurements were obtained prior to transcatheter pulmonary valve replacement, immediately after transcatheter pulmonary valve replacement, and within 6 months to 1 year after transcatheter pulmonary valve replacement. Right ventricular annular tilt measures the angle of the tricuspid valve plane relative to the mitral valve plane at end-diastole in the apical four-chamber view. Right ventricular fractional area change, right ventricular systolic strain, tissue Doppler velocity, and tricuspid annular plane systolic excursion Z-scores were obtained using published methods. RESULTS: Right ventricular annular tilt decreased significantly immediately after transcatheter pulmonary valve replacement (p = 0.0004), and this reduction in right ventricular volume persisted at the mid-term follow-up (p < 0.0001). Fractional area change did not change significantly after transcatheter pulmonary valve replacement while right ventricular global strain improved at mid-term follow-up despite no significant difference immediately after transcatheter pulmonary valve replacement. CONCLUSIONS: Right ventricular annular tilt decreases both immediately after transcatheter pulmonary valve replacement and at mid-term follow-up. Right ventricular strain also improved after transcatheter pulmonary valve replacement, corresponding to the improved volume load. Right ventricular annular tilt can be considered as an additional echocardiographic factor to assess right ventricular volume and remodeling after transcatheter pulmonary valve replacement.

Biomonitoring of mercury and selenium in commercially important shellfish: Distribution pattern, health benefit assessment and consumption advisories.

This study aims to explore the concentrations of Se and Hg in shellfish along the Gulf of Mannar (GoM) coast (Southeast India) and to estimate related risks and risk-based consumption limits for children, pregnant women, and adults. Se concentrations in shrimp, crab, and cephalopods ranged from 0.256 to 0.275 mg kg-1, 0.182 to 0.553 mg kg-1, and 0.176 to 0.255 mg kg-1, respectively, whereas Hg concentrations differed from 0.009 to 0.014 mg kg-1, 0.022 to 0.042 mg kg-1 and 0.011 to 0.024 mg kg-1, respectively. Se and Hg content in bamboo shark (C. griseum) was 0.242 mg kg-1 and 0.082 mg kg-1, respectively. The lowest and highest Se concentrations were found in C. indicus (0.176 mg kg-1) and C. natator (0.553 mg kg-1), while Hg was found high in C. griseum (0.082 mg kg-1) and low in P. vannamei (0.009 mg kg-1). Se shellfishes were found in the following order: crabs > shrimp > shark > cephalopods, while that of Hg were shark > crabs > cephalopods > shrimp. Se in shellfish was negatively correlated with trophic level (TL) and size (length and weight), whereas Hg was positively correlated with TL and size. Hg concentrations in shellfish were below the maximum residual limits (MRL) of 0.5 mg kg-1 for crustaceans and cephalopods set by FSSAI, 0.5 mg kg-1 for crustaceans and 1.0 mg kg-1 for cephalopods and sharks prescribed by the European Commission (EC/1881/2006). Se risk-benefit analysis, the AI (actual intake):RDI (recommended daily intake) ratio was > 100%, and the AI:UL (upper limit) ratio was < 100%, indicating that all shellfish have sufficient level of Se to meet daily requirements without exceeding the upper limit (UL). The target hazard quotient (THQ < 1) and hazard index (HI < 1) imply that the consumption of shellfish has no non-carcinogenic health impacts for all age groups. However, despite variations among the examined shellfish, it was consistently observed that they all exhibited a Se:Hg molar ratio > 1. This finding implies that the consumption of shellfish is generally safe in terms of Hg content. The health benefit indexes, Se-HBV and HBVse, consistently showed high positive values across all shellfish, further supporting the protective influence of Se against Hg toxicity and reinforcing the overall safety of shellfish consumption. Enhancing comprehension of food safety analysis, it is crucial to recognize that the elevated Se:Hg ratio in shellfish may be attributed to regular selenoprotein synthesis and the mitigation of Hg toxicity by substituting Se bound to Hg.

Global spatial distribution of Prosopis juliflora - one of the world's worst 100 invasive alien species under changing climate using multiple machine learning models.

Climate change is one of the factors contributing to the spread of invasive alien species. As a result, it is critical to investigate potential invasion dynamics on a global scale in the face of climate change. We used updated occurrence data, bioclimatic variables, and Köppen-Geiger climatic zones to better understand the climatic niche dynamics of Prosopis juliflora L. (Fabaceae). In this study, we first compared several algorithms-MaxEnt, generalized linear model (GLM), artificial neural network (ANN), generalized boosted model (GBM), generalized additive model (GAM), and random forest (RF)-to investigate the relationships between species-environment and climate for mesquite. We identified the global climate niche similarity sites (NSSs) using the coalesce approach. This study focused on the current and future climatic suitability of P. juliflora under two global circulation models (GCMs) and two climatic scenarios, i.e., Representative Concentration Pathways (RCPs), 4.5 and 8.5, for 2050 and 2070, respectively. Sensitivity, specificity, true skill statistic (TSS), kappa coefficient, and correlation were used to evaluate model performance. Among the tested models, the machine learning algorithm random forest (RF) demonstrated the highest accuracy. The vast swaths of currently uninvaded land on multiple continents are ideal habitats for invasion. Approximately 9.65% of the area is highly suitable for the establishment of P. juliflora. Consequently, certain regions in the Americas, Africa, Asia, Europe, and Oceania have become particularly vulnerable to invasion. In relation to RCPs, we identified suitable area changes (expansion, loss, and stability). The findings of this study show that NSSs and RCPs increase the risk of invasion in specific parts of the world. Our findings contribute to a cross-border continental conservation effort to combat P. juliflora  expansion into new potential invasion areas.

Molecular dynamics studies of CED-4/CED-9/EGL-1 ternary complex reveal CED-4 release mechanism in the linear apoptotic pathway of Caenorhabditis elegans.

Many steps in programmed cell death are evolutionarily conserved across different species. The Caenorhabditis elegans proteins CED-9, CED-4 and EGL-1 involved in apoptosis are respectively homologous to anti-apoptotic Bcl-2 proteins, Apaf-1 and the "BH3-only" pro-apototic proteins in mammals. In the linear apoptotic pathway of C. elegans, EGL-1 binding to CED-9 leads to the release of CED-4 from CED-9/CED-4 complex. The molecular events leading to this process are not clearly elucidated. While the structures of CED-9 apo, CED-9/EGL-1 and CED-9/CED-4 complexes are known, the CED-9/CED-4/EGL-1 ternary complex structure is not yet determined. In this work, we modeled this ternary complex and performed molecular dynamics simulations of six different systems involving CED-9. CED-9 displays differential dynamics depending upon whether it is bound to CED-4 and/or EGL-1. CED-4 exists as an asymmetric dimer (CED4a and CED4b) in CED-9/CED-4 complex. CED-4a exhibits higher conformational flexibility when simulated without CED-4b. Principal Component Analysis revealed that the direction of CED-4a's winged-helix domain motion differs in the ternary complex. Upon EGL-1 binding, majority of non-covalent interactions involving CARD domain in the CED-4a-CED-9 interface have weakened and only half of the contacts found in the crystal structure between α/ß domain of CED4a and CED-9 are found to be stable. Additional stable contacts in the ternary complex and differential dynamics indicate that winged-helix domain may play a key role in CED-4a's dissociation from CED-9. This study has provided a molecular level understanding of potential intermediate states that are likely to occur when CED-4a is released from CED-9.

Unraveling different begomoviruses, DNA satellites and cryptic species of Bemisia tabaci and their endosymbionts in vegetable ecosystem.

Bemisia tabaci species complex contains more than 46 cryptic species. It has emerged as an important pest causing significant yield loss in many cultivated crops. This pest is also a vector for more than 100 species of begomoviruses, that are a major threat for the cultivation of many crops in different regions of the world. The relation between cryptic species of the B. tabaci species complex and associated begomoviruses that infect different crops remains unclear. In the present study, four cryptic species (Asia I, China 3, Asia II 5 and Asia II-1) of B. tabaci and four associated endosymbionts (Arsenophonus, Cardinium, Rickettsia and Wolbachia) were identified in different vegetable crops. The vector-based PCR detection revealed five different begomoviruses such as okra enation leaf curl virus (OELCuV), tomato leaf curl Palampur virus (ToLCPalV), squash leaf curl China virus (SLCCNV), chilli leaf curl virus (ChiLCuV), and tomato leaf curl New Delhi virus (ToLCNDV). Of these begomoviruses, the maximum infection rate was observed (9.1%) for OELCuV, followed by 7.3% for ToLCNDV. The infection rate of the other three viruses (SLCCNV, ChiLCuV, ToLCPalV) ranged from 0.9 to 2.7% in cryptic species of B. tabaci. Further, each cryptic species was infected with multiple virus species and the virus infection rate of Asia I, Asia II-5, China 3 and Asia II-1 was 21.2%, 15.1%, 15.1% and 0.6% respectively. Similarly, in case of betasatellites the highest infection rate was 12% for ToLCBDB, followed by 6% for OLCuB and PaLCB. With regard to alphasatellites, the highest infection rate was 18.2% for AEV and 3% for CLCuMuA. This study demonstrates the distribution of cryptic species of whitefly and their endosymbionts, and associated begomoviruses and DNA satellites in vegetable ecosystem. We believe that the information generated here is useful for evolving an effective pest management strategies for vegetable production.

Diversity and phylogeography of begomoviruses and DNA satellites associated with the leaf curl and mosaic disease complex of eggplant.

Eggplant is one of the important vegetable crops grown across the world, and its production is threatened by both biotic and abiotic stresses. Diseases caused by viruses are becoming major limiting factors for its successful cultivation. A survey for begomovirus-like symptoms in 72 eggplant fields located in six different Indian states revealed a prevalence of disease ranging from 5.2 to 40.2%, and the symptoms recorded were mosaic, mottling, petiole bending, yellowing, and upward curling, vein thickening, and enation of the leaves, and stunting of plants. The causal agent associated with these plants was transmitted from infected leaf samples to healthy eggplant seedlings via grafting and whiteflies (Bemisia tabaci). The presence of begomovirus was confirmed in 72 infected eggplant samples collected from the surveyed fields exhibiting leaf curl and mosaic disease by PCR using begomovirus specifc primers (DNA-A componet), which resulted in an expected amplicon of 1.2 kb. The partial genome sequence obtained from amplified 1.2 kb from all samples indicated that they are closely related begomovirus species, tomato leaf Karnataka virus (ToLCKV, two samples), tomato leaf curl Palampur virus (ToLCPalV, fifty eggplant samples), and chilli leaf curl virus (ChLCuV, twenty samples). Based on the partial genome sequence analysis, fourteen representative samples were selected for full viral genome amplification by the rolling circle DNA amplification (RCA) technique. Analyses of fourteen eggplant isolates genome sequences using the Sequence Demarcation Tool (SDT) indicated that one isolate had the maximum nucleotide (nt) identity with ToLCKV and eight isolates with ToLCPalV. Whereas, four isolates four isolates (BLC1-CH, BLC2-CH, BLC3-CH, BLC4-CH) are showing nucleotide identity of less than 91% with chilli infecting viruses begomoviruses with chilli infecting begomoviruses and as per the guidelines given by the ICTV study group for the classification of begomoviruses these isolates are considered as one novel begomovirus species, for which name, Eggplant leaf curl Chhattisgarh virus (EgLCuChV) is proposed. For DNA-B component, seven eggplant isolates had the highest nt identity with ToLCPalV infecting other crops. Further, DNA satellites sequence analysis indicated that four betasatellites identified shared maximum nucleotide identity with the tomato leaf curl betasatellite and five alphasatellites shared maximum nucleotide identity with the ageratum enation alphasatellite. Recombination and GC plot analyses indicated that the bulk of begomovirus genome and associated satellites presumably originated from of previously known mono and bipartite begomoviruses and DNA satellites. To the best of our knowledge, this is India's first report of ToLCKV and a noval virus, eggplant leaf curl Chhattisgarh virus associated with eggplant leaf curl disease.

Toxicological effect of endocrine disrupting heavy metal (Pb) on Mekong silurid Pangasius catfish, Pangasius hypophthalmus.

The current study aimed to investigate the effects of lead nitrate exposure on the enzymatical, haematological, and histological changes in the gill, liver, and kidney of Pangasius hypophthalmus. The fish were divided into six groups and treated with different Pb concentrations. The LC50 value of Pb was 55.57 mg/L at 96 h for P. hypophthalmus, and sublethal toxicity was assessed for 45 days at 1/5th (11.47 mg/L) and 1/10th (5.57 mg/L) of LC50 concentration. Enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, alkaline phosphate (ALP), and lactate dehydrogenase (LDH) content increased significantly during sublethal toxicity of Pb. The reduction of HCT and PCV indicates an anemic condition due to the toxicity of Pb. Differential leucocytes, lymphocytes, and monocytes and their % values significantly decreased, indicating Pb exposure. The main histological changes observed in the gills were the destruction of secondary lamellae, the fusion of adjacent gill lamellae, primary lamellae hypertrophy, and severe hyperplasia, while in kidney exposed to Pb showed melanomacrophages, increased periglomerular, peritubular space, vacuolation, shrunken glomerulus, destruction of tubular epithelium, and hypertrophy of distal convoluted segment. The liver showed severe necrosis and rupture of hepatic cells, hyper trepheoid bile duct, shifting of nuclei, and vascular hemorrhage, while in the brain, binucleus, mesoglea cells, vacuole, and ruptured nucleus were observed. In conclusion, P. hypophthalmus, which has been exposed to Pb has developed a number of toxicity markers. Consequently, prolonged exposure to higher Pb concentrations may be harmful to fish health. The findings strongly suggest that the lead had a detrimental impact on the P. hypophthalmus population, as well as on the water quality and non-target aquatic organisms.

Effect of dietary supplementation of organic and inorganic Se on performance and antioxidant response in commercial broiler chickens.

1. The study was carried out to determine the effects of supplementing organic (OG) or inorganic (IOG) Se to record the performance, immune and anti-oxidant response in broiler chickens.2. One-day-old Vencobb-400 (50.1 ± 0.84 g; n = 280) male broiler chicks were allocated randomly into seven treatments to give eight replicates containing five chicks each and housed in deep littered floor pens (76 cm × 91 cm) for a period of 42 d.3. The control diet (CD) was formulated without any Se supplementation (diet I), CD plus 0.15, 0.30 or 0.45 mg/kg OG Se (diets II, III and IV, respectively) and CD plus 0.15, 0.30 or 0.45 mg/kg IOG Se (diets V, VI and VII, respectively).4. Feed intake (FI), body weight gain (BWG), immune variables and mRNA expression profile of hepatic selenoproteins (SepW, GSHPx1, TrxR and GSHPx3) genes were determined. The BWG, FI and feed conversion ratio did not differ among various dietary treatments.5. The lipid peroxidation and activity of RBC catalase were lower (P < 0.05) in groups fed diets supplemented OG Se compared to those fed IOG Se and CD. The activity of GSH Px was higher among the groups fed diet supplemented OG Se compared to those groups fed OG Se and CD. However, supplementing diets with OG or IOG Se did not affect humoral or cell mediated immune responses.6. The expression levels of SepW were higher (P < 0.01) among the groups supplemented with OG Se. Expression levels of GSH-Px1, TrxR and GSHPx3 were higher (P < 0.01) among the groups supplemented with OG Se compared to those groups fed IOG Se or CD.7. Supplementing OG Se improved the activities of anti-oxidant enzymes and hepatic expression of selenoproteins genes in the present study. However, supplementing OG or IOG Se did not affect growth performance and immune variables in broiler chickens.

Rubber expansion and age-class mapping in the state of Tripura (India) 1990-2021 using multi-year and multi-sensor data.

The present study focuses on the spread of rubber monoculture in the state of Tripura during past three decades (1990-2021) in the northeast region of India which is known for its rich biodiversity, shifting cultivation, and extensive forest dynamics. Earth observation (EO) data of seven time periods from Landsat missions (1990, 1995, 2000, 2004, and 2009) and Sentinel-2 (2016 and 2021) were the main source for mapping and were supplemented with MODIS-EVI temporal spectral profiles, GEDI-derived vegetation heights (2019), and Google Earth high-resolution historical images for additional cues to support discrimination, mapping, and accuracy assessment. The methodology for rubber used its unique phenology from spectral-temporal profile and multi-year comparison of patches and their dynamics for age-class mapping. The results indicate that in the state of Tripura (geographic area 1.08 Mha), the area under rubber increased from 0.3% in 1990 to 8.9% of the geographic area in 2021. The overall classification accuracy for the maps created for the years 1990, 1995, 2000, 2004, 2009, 2016, and 2021 was 84.2%, 83.9%, 84.8%, 88.0%, 86.0%, 86.7%, and 89.5%, respectively. New areas under rubber originated from various land cover classes including open forests, shifting cultivation lands, and scrub. Recent expansion has resulted in 84.3% of rubber plantations under the 10-year age class. Implications of this transformation of the natural landscape, biodiversity and biomass, and carbon pool assessment are discussed.

Viscoelastic Covalent Organic Nanotube Fabric via Macroscopic Entanglement.

Covalent organic nanotubes (CONTs) are one-dimensional porous frameworks constructed from organic building blocks via dynamic covalent chemistry. CONTs are synthesized as insoluble powder that restricts their potential applications. The judicious selection of 2,2'-bipyridine-5,5'-dicarbaldehyde and tetraaminotriptycene as building blocks for TAT-BPy CONTs has led to constructing flexible yet robust and self-standing fabric up to 3 µm thickness. The TAT-BPy CONTs and TAT-BPy CONT fabric have been characterized by solid-state one-dimensional (1D) 13C CP-MAS, two-dimensional (2D) 13C-1H correlation NMR, 2D 1H-1H DQ-SQ NMR, and 2D 14N-1H correlation NMR spectroscopy. The mechanism of fabric formation has been established by using high-resolution transmission electron microscopy and scanning electron microscopy techniques. The as-synthesized viscoelastic TAT-BPy CONT fabric exhibits high mechanical strength with a reduced modulus (Er) of 8 (±3) GPa and hardness (H) of 0.6 (±0.3) GPa. Interestingly, the viscoelastic fabric shows time-dependent elastic depth recovery up to 50-70%.

Dual Nanomechanics in Anisotropic Porous Covalent Organic Framework Janus-Type Thin Films.

Empowered by crystalline ordered structures and homogeneous fabrication techniques, covalent organic frameworks (COFs) have been realized with uniform morphologies and isotropic properties. However, such homogeneity often hinders various surface-dependent properties observed in asymmetric nanostructures. The challenge remains to induce heterogeneity in COFs by creating an asymmetric superstructure such as a Janus thin film. In this regard, we propose a versatile yet straightforward interfacial layer-grafting strategy to fabricate free-standing Janus-type COF-graphene thin films. Herein, two-dimensional graphene sheets were utilized as the suitable grafter due to the possibility of noncovalent interactions between the layers. The versatility of the approach was demonstrated by fabricating two distinct Janus-type films, with the COF surface interwoven with nanofibers and nanospheres. The Janus-type films showcase opposing surface morphologies originating from graphene sheets and COF nanofibers or nanospheres, preserving the porosity (552-600 m2 g-1). The unique surface chemistries of the constituent layers further endow the films with orthogonal mechanical properties, as confirmed by the nanoindentation technique. Interestingly, the graphene sheets favor the Janus-type assembly of COF nanofibers over the nanospheres. This is reflected in the better nanomechanical properties of COFfiber-graphene films (Egraphene = 300-1200 MPa; ECOF = 15-60 MPa) compared to the COFsphere-graphene films (Egraphene = 11-14 MPa; ECOF = 2-5 MPa). These results indicate a direct relationship between the mechanical properties and homo/heterogeneity of Janus-type COF films.

g-C3N4 nanosheets functionalized yttrium-doped ZrO2 nanoparticles for efficient photocatalytic Cr(VI) reduction and energy storage applications.

Novel g-C3N4 functionalized yttrium-doped ZrO2 hybrid heterostructured (g-YZr) nanoparticles have been synthesized to investigate photocatalytic Cr(VI) reduction as well as electrochemical energy storage applications. The nanoparticles have been characterized to examine their structural, optical, and photocatalytic properties. XRD confirmed the incorporation of dopant ions and heterostructure development between g-C3N4 and doped ZrO2. When g-C3N4 was doped with ZrO2, the ability of light adsorption was greatly enhanced due to the narrow band gap. The distinctive structure of g-YZr exhibited outstanding photocatalytic Cr(VI) reduction owing to its superior surface area, which greatly prevented the charge carriers' recombination rate and exhibited superior photocatalytic performance within 90 min of solar light irradiation. Furthermore, these catalysts demonstrated similar catalytic Cr(VI) reduction activity following four repeatability tests, indicating the exceptional structural stability of g-YZr catalysts. The electrochemical performance of the electrodes revealed that g-YZr exhibited superior specific capacitance over the other electrodes owing to extra energetic sites and robust synergic effect. Enhanced specific capacitance and long cyclic stability of the hybrid heterostructures displayed their usefulness for energy storage applications.

Gut-Brain Axis, Neurodegeneration and Mental Health: A Personalized Medicine Perspective.

Neurological conditions such as neurodegenerative diseases and mental health disorders are a result of multifactorial underpinnings, leading to individual-based complex phenotypes. Demystification of these multifactorial connections will promote disease diagnosis and treatment. Personalized treatment rather than a one-size-fits-all approach would enable us to cater to the unmet healthcare needs based on protein-protein and gene-environment interactions. Gut-brain axis, as the name suggests, is a two-way biochemical communication pathway between the central nervous system (CNS) and enteric nervous system (ENS), enabling a mutual influence between brain and peripheral intestinal functions. The gut microbiota is a major component of this bidirectional communication, the composition of which is varied depending on the age, and disease conditions, among other factors. Gut microbiota profile is typically unique and personalized therapeutic intervention can aid in treating or delaying neurodegeneration and mental health conditions. Besides, research on the gut microbial influence on these conditions is gaining attention, and a better understanding of this concept can lead to identification of novel targeted therapies.

Significance of Laboratory Markers in Predicting the Severity of COVID-19 in the Central Reserve Police Force Front-line Workers with a Review of Literature.

COVID-19 disease has variable clinical presentations, ranging from asymptomatic to mild symptoms to severe manifestation with pneumonia, acute respiratory distress syndrome, septic shock, disseminated intravascular coagulation, and/or multiple organ failure. The real-time reverse transcription-polymerase chain reaction is gold standard test for severe acute respiratory syndrome-coronavirus-2 detection. In the present study, we aimed to predict the significance of various hematological and biochemical markers for early identification of complications and assessing the severity of the disease. A total of cases were divided into two study groups, namely, severe and nonsevere based on clinical presentation. Out of 210 cases, 186 (88.5%) cases were nonsevere and 24 (11.5%) cases were severe. Among various hematological and biochemical markers studied, hemoglobin, total leukocyte count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, albumin, lactate dehydrogenase, C-reactive protein, ferritin, D-dimer, and interleukin-6 are found to have P < 0.05 and significantly correlated with the severity of disease.

Temperature-Reliant Dynamic Properties and Elasto-Plastic to Plastic Crystal (Rotator) Phase Transition in a Metal Oxyacid Salt.

Although, dynamic crystals are attractive for use in many technologies, molecular level mechanisms of various solid-state dynamic processes and their interdependence, remain poorly understood. Here, we report a rare example of a dynamic crystal (1), involving a heavy transition metal, rhenium, with an initial two-face elasticity (within ≈1 % strain), followed by elasto-plastic deformation, at room temperature. Further, these crystals transform to a rotator (plastic) crystal phase at ≈105 °C, displaying exceptional malleability. Qualitative and quantitative mechanical tests, X-ray diffraction, µ-Raman and polarized light microscopy experiments reveal that the elasto-plastic deformation involves both partial molecular rotations and slip, while malleability in the rotator phase is facilitated by reorientational motions and increased symmetry (slip planes). Our work, connecting the plastically bendable (1D or 2D) crystals with the rotator phases (3D), is important for designing multi-functional dynamic crystals.

Self-Assembly-Driven Nanomechanics in Porous Covalent Organic Framework Thin Films.

Nanomechanics signifies a key tool to interpret the macroscopic mechanical properties of a porous solid in the context of molecular-level structure. However, establishing such a correlation has proved to be significantly challenging in porous covalent organic frameworks (COFs). Structural defects or packing faults within the porous matrix, poor understanding of the crystalline assembly, and surface roughness are critical factors that contribute to this difficulty. In this regard, we have fabricated two distinct types of COF thin films by controlling the internal order and self-assembly of the same building blocks. Interestingly, the defect density and the nature of supramolecular interactions played a significant role in determining the corresponding thin films' stress-strain behavior. Thin films assembled from nanofibers (∼1-2 µm) underwent large deformation on the application of small external stress (Tp-Azofiber film: E ≈ 1.46 GPa; H ≈ 23 MPa) due to weak internal forces. On the other hand, thin films threaded with nanospheres (∼600 nm) exhibit a much stiffer and harder mechanical response (Tp-Azosphere film: E ≈ 15.3 GPa; H ≈ 66 MPa) due to strong covalent interactions and higher crystallinity. These porous COF films further exhibited a significant elastic recovery (∼80%), ideal for applications dealing with shock-resistant materials. This work provides in-depth insight into the fabrication of industrially relevant crystalline porous thin films and membranes by addressing the previously unanswered questions about the mechanical constraints in COFs.

Investigation of Poor Solubility of a Salt-Cocrystal Hydrate: A Case Study of the Common-Ion Effect in Betrixaban, an Anticoagulant Drug.

Achieving the desired solubility and dissolution of active pharmaceutical ingredients (APIs) continues to be a big challenge in the pharmaceutical industry. In this regard, multicomponent solids of APIs such as salts and cocrystals have shown significant promise in resolving such solubility/dissolution issues. However, very little is known on how the APIs' solubility or dissolution is affected by the drug to coformer ratio in multicomponent solids. Betrixaban, is an anticoagulant drug approved in 2017 for the prevention of venous thromboembolism. During the alternate solid form development studies of the known betrixaban maleate, a rare multicomponent solid form, salt-cocrystal hydrate of betrixaban, was discovered and characterized thoroughly by spectroscopic, thermal, and X-ray crystallographic methods. Significantly, the new betrixaban maleate maleic acid hydrate (1:1:2:1) form has shown lower melting point (80 °C) as compared to its parent salt (197.5 °C). From such a large melting difference (117 °C) between the salt and salt-cocrystal hydrate of API, we anticipated substantially better solubility for the salt-cocrystal hydrate (low enthalpy). Furthermore, the predicted solubility also supported our anticipation. However, the powder dissolution tests at different pH conditions provided contrary results, that is, the salt-cocrystal hydrate showed 10 times lower solubility as compared to its salt. A detailed investigation, considering all the potential factors, revealed that "common-ion effect" could be a critical factor for the low solubility of the salt-cocrystal hydrate in which the API to coformer ratio is 1:3. To the best of our knowledge, this is the first case study on the solubility of pharmaceutical salt-cocrystal hydrates with an emphasis on "common-ion effect" or drug to coformer ratio.