Clinical genomics expands the link between erroneous cell division, primary microcephaly and intellectual disability.

Primary microcephaly is a rare neurogenic and genetically heterogeneous disorder characterized by significant brain size reduction that results in numerous neurodevelopmental disorders (NDD) problems, including mild to severe intellectual disability (ID), global developmental delay (GDD), seizures and other congenital malformations. This disorder can arise from a mutation in genes involved in various biological pathways, including those within the brain. We characterized a recessive neurological disorder observed in nine young adults from five independent consanguineous Pakistani families. The disorder is characterized by microcephaly, ID, developmental delay (DD), early-onset epilepsy, recurrent infection, hearing loss, growth retardation, skeletal and limb defects. Through exome sequencing, we identified novel homozygous variants in five genes that were previously associated with brain diseases, namely CENPJ (NM_018451.5: c.1856A > G; p.Lys619Arg), STIL (NM_001048166.1: c.1235C > A; p.(Pro412Gln), CDK5RAP2 (NM_018249.6 c.3935 T > G; p.Leu1312Trp), RBBP8 (NM_203291.2 c.1843C > T; p.Gln615*) and CEP135 (NM_025009.5 c.1469A > G; p.Glu490Gly). These variants were validated by Sanger sequencing across all family members, and in silico structural analysis. Protein 3D homology modeling of wild-type and mutated proteins revealed substantial changes in the structure, suggesting a potential impact on function. Importantly, all identified genes play crucial roles in maintaining genomic integrity during cell division, with CENPJ, STIL, CDK5RAP2, and CEP135 being involved in centrosomal function. Collectively, our findings underscore the link between erroneous cell division, particularly centrosomal function, primary microcephaly and ID.

IAA is more effective than EDTA in enhancing phytoremediation potential for cadmium and copper contaminated soils.

Enhanced phytoremediation offers a rapid and eco-friendly approach for cleaning agricultural soil contaminated with copper and cadmium which pose a direct threat to food scarcity and security. The current study aimed to compare the effectiveness of the two commonly used additives, IAA and EDTA, for the remediation of copper (Cu) and cadmium (Cd) contaminated soils using sunflower and maize. The plants were cultivated in pots under controlled conditions with four sets of treatments: control (0), Cu50/Cd50, Cu50/Cd50 + EDTA, and Cu50/Cd50 + IAA. The results showed that Cu50/Cd50 mg/kg drastically compromised the phytoremediation potential of both plants, as evident by reduced shoot and root length, and lower biomass. However, the augmentation of Cu50/Cd50 with EDTA or IAA improved the tested parameters. In sunflower, EDTA enhanced the accumulation of Cu and Cd by 58% and 21%, respectively, and improved plant biomass by 41%, compared to control treatment. However, IAA exhibited higher accumulation of Cu and Cd by 64% and 25%, respectively, and enhanced plant biomass by 43%. In case of maize, IAA was superior to EDTA which enhanced the accumulation of Cu and Cd by 87% and 32% respectively, and increased the plant biomass by 57%, compared to control treatment. Our findings demonstrate that foliar IAA is more effective than EDTA in enhancing the phytoremediation potential of sunflower and maize for Cu and Cd.

Phosphate solubilizing Aspergillus Niger PH1 ameliorates growth and alleviates lead stress in maize through improved photosynthetic and antioxidant response.

Among the several threats to humanity by anthropogenic activities, contamination of the environment by heavy metals is of great concern. Upon entry into the food chain, these metals cause serious hazards to plants and other organisms including humans. Use of microbes for bioremediation of the soil and stress mitigation in plants are among the preferred strategies to provide an efficient, cost-effective, eco-friendly solution of the problem. The current investigation is an attempt in this direction where fungal strain PH1 was isolated from the rhizosphere of Parthenium hysterophorus which was identified as Aspergillus niger by sequence homology of the ITS 1 and ITS 4 regions of the rRNA. The strain was tested for its effect on growth and biochemical parameters as reflection of its potential to mitigate Pb stress in Zea mays exposed to 100, 200 and 500 µg of Pb/g of soil. In the initial screening, it was revealed that the strain has the ability to tolerate lead stress, solubilize insoluble phosphate and produce plant growth promoting hormones (IAA and SA) and other metabolites like phenolics, flavonoids, sugar, protein and lipids. Under 500 µg of Pb/g of soil, Z. mays exhibited significant growth retardation with a reduction of 31% in root length, 30.5% in shoot length, 57.5% in fresh weight and 45.2% in dry weight as compared to control plants. Inoculation of A. niger to Pb treated plants not only restored root and shoot length, rather promoted it to a level significantly higher than the control plants. Association of the strain modulated the physio-hormonal attributes of maize plants that resulted in their better growth which indicated a state of low stress. Additionally, the strain boosted the antioxidant defence system of the maize there by causing a significant reduction in the ascorbic acid peroxidase (1.5%), catalase (19%) and 1,1-diphenyl-2 picrylhydrazyl (DPPH) radical scavenging activity (33.3%), indicating a lower stress condition as compared to their non-inoculated stressed plants. Based on current evidence, this strain can potentially be used as a biofertilizer for Pb-contaminated sites where it will improve overall plant health with the hope of achieving better biological and agricultural yields.

Xanthan gum-based edible coating effectively preserve postharvest quality of 'Gola' guava fruits by regulating physiological and biochemical processes.

BACKGROUND: Guava is a fruit prone to rapid spoilage following harvest, attributed to continuous and swift physicochemical transformations, leading to substantial postharvest losses. This study explored the efficacy of xanthan gum (XG) coatings applied at various concentrations (0.25, 0.5, and 0.75%) on guava fruits (Gola cultivar) over a 15-day storage period. RESULTS: The results indicated that XG coatings, particularly at 0.75%, substantially mitigated moisture loss and decay, presenting an optimal concentration. The coated fruits exhibited a modified total soluble soluble solids, an increased total titratable acidity, and an enhanced sugar-acid ratio, collectively enhancing overall quality. Furthermore, the XG coatings demonstrated the remarkable ability to preserve bioactive compounds, such as total phenolics, flavonoids, and antioxidants, while minimizing the levels of oxidative stress markers, such as electrolyte leakage, malondialdehyde, and H2O2. The coatings also influenced cell wall components, maintaining levels of hemicellulose, cellulose, and protopectin while reducing water-soluble pectin. Quantitative analysis of ROS-scavenging enzymes, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, revealed significant increases in their activities in the XG-coated fruits compared to those in the control fruits. Specifically, on day 15, the 0.75% XG coating demonstrated the highest SOD and CAT activities while minimizing the reduction in APX activity. Moreover, XG coatings mitigated the activities of fruit-softening enzymes, including pectin methylesterase, polygalacturonase, and cellulase. CONCLUSIONS: This study concludes that XG coatings play a crucial role in preserving postharvest quality of guava fruits by regulating various physiological and biochemical processes. These findings offer valuable insights into the potential application of XG as a natural coating to extend the shelf life and maintain the quality of guava fruits during storage.

Rejuvenating potato growth and yield in challenging semiarid and saline sandy Cholistan: harnessing PGPB-coated N and P application strategies.

BACKGROUND: Potato serves as a major non-cereal food crop and income source for small-scale growers in Punjab, Pakistan. Unfortunately, improper fertilization practices have led to low crop yields, worsened by challenging environmental conditions and poor groundwater quality in the Cholistan region. To address this, we conducted an experiment to assess the impact of two fertilizer application approaches on potato cv. Barna using plant growth-promoting bacteria (PGPB) coated biofertilizers. The first approach, termed conventional fertilizer application (CFA), involved four split applications of PGPB-coated fertilizers at a rate of 100:75 kg acre-1 (N and P). The second, modified fertilizer application (MFA), employed nine split applications at a rate of 80:40 kg acre-1. RESULTS: The MFA approach significantly improved various plant attributes compared to the CFA. This included increased plant height (28%), stem number (45%), leaf count (46%), leaf area index (36%), leaf thickness (three-folds), chlorophyll content (53%), quantum yield of photosystem II (45%), photosynthetically active radiations (56%), electrochromic shift (5.6%), proton flux (24.6%), proton conductivity (71%), linear electron flow (72%), photosynthetic rate (35%), water use efficiency (76%), and substomatal CO2 (two-folds), and lowered non-photochemical quenching (56%), non-regulatory energy dissipation (33%), transpiration rate (59%), and stomatal conductance (70%). Additionally, the MFA approach resulted in higher tuber production per plant (21%), average tuber weight (21.9%), tuber diameter (24.5%), total tuber yield (29.1%), marketable yield (22.7%), seed-grade yield (9%), specific gravity (9.6%), and soluble solids (7.1%). It also reduced undesirable factors like goli and downgrade yields by 57.6% and 98.8%, respectively. Furthermore, plants under the MFA approach exhibited enhanced nitrogen (27.8%) and phosphorus uptake (40.6%), with improved N (26.1%) and P uptake efficiency (43.7%) compared to the CFA approach. CONCLUSION: The use of PGPB-coated N and P fertilizers with a higher number of splits at a lower rate significantly boosts potato production in the alkaline sandy soils of Cholistan.

Halotolerant Pseudomonas koreensis S4T10 mitigate salt and drought stress in Arabidopsis thaliana.

Salt and drought are documented among the most detrimental and persistent abiotic stresses for crop production. Here, we investigated the impact of Pseudomonas koreensis strain S4T10 on plant performance under salt and drought stress. Arabidopsis thaliana Col-0 wild type and atnced3 mutant plants were inoculated with P. koreensis or tap water and exposed to NaCl (100 mM) for five days and drought stress by withholding water for seven days. P. koreensis significantly enhanced plant biomass and photosynthetic pigments under salt and drought stress conditions. Moreover, P. koreensis activated the antioxidant defence by modulating glutathione (GSH), superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activities to scavenge the reactive oxygen species produced due to the stress. In addition, the application of P. koreensis upregulated the expression of genes associated with antioxidant responses, such as AtCAT1, AtCAT3, and AtSOD. Similarly, genes linked to salt stress, such as AtSOS1, AtSOS2, AtSOS3, AtNHX1, and AtHKT1, were also upregulated, affirming the positive role of P. koreensis S4T10 in streamlining the cellular influx and efflux transport systems during salt stress. Likewise, the PGPB inoculation was observed to regulate the expression of drought-responsive genes AtDREB2A, AtDREB2B, and ABA-responsive genes AtAO3, AtABA3 indicating that S4T10 enhanced drought tolerance via modulation of the ABA pathway. The results of this study affirm that P. koreensis S4T10 could be further developed as a biofertilizer to mitigate salt and drought stress at the same time.

In silico homology modeling of dengue virus non-structural 4B (NS4B) protein and its molecular docking studies using triterpenoids.

BACKGROUND: Dengue fever has become a significant worldwide health concern, because of its high morbidity rate and the potential for an increase in mortality rates due to lack of adequate treatment. There is an immediate need for the development of effective medication for dengue fever. METHODS: Homology modeling of dengue virus (DENV) non-structural 4B (NS4B) protein was performed by SWISS-MODEL to predict the 3D structure of the protein. Structure validation was conducted using PROSA, PROCHECK, Ramachandran plot, and VERIFY-3D. MOE software was used to find out the in-Silico inhibitory potential of the five triterpenoids against the DENV-NS4B protein. RESULTS: The SWISS-MODEL was employed to predict the three-dimensional protein structure of the NS4B protein. Through molecular docking, it was found that the chosen triterpenoid NS4B protein had a high binding affinity interaction. It was observed that the NS4B protein binding energy for 15-oxoursolic acid, betulinic acid, ursolic acid, lupeol, and 3-o-acetylursolic acid were - 7.18, - 7.02, - 5.71, - 6.67 and - 8.00 kcal/mol, respectively. CONCLUSIONS: NS4B protein could be a promising target which showed good interaction with tested triterpenoids which can be developed as a potential antiviral drug for controlling dengue virus pathogenesis by inhibiting viral replication. However, further investigations are necessary to validate and confirm their efficacy.

Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors.

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

The risk paradox: Exploring asymmetric nexus between climate policy uncertainty and renewable energy technology budgets.

The ups and downs of climate policy uncertainty (CPU) cast a captivating shadow over the budgets allocated to renewable energy (RE) technologies, where strategic choices and risk assessment will determine the course of our green environmental revolution. The main intention of this investigation is to scrutinize the effect of CPU on the RE technology budgets (RETBs) in the top 10 countries with the highest RE research and development budgets (the USA, China, South Korea, India, Germany, the United Kingdom, France, Japan, Australia, and Italy). Although former researchers have typically employed panel data tools to contemplate the connection between CPU and RE technology, they repeatedly ignored variations in this connection throughout different economies. In contrast, our research adopts a unique approach, "quantile-on-quantile," to check this association at the country-to-country level. This approach offers a comprehensive worldwide perspective while procuring tailor-made perceptions for individual economies. The outcomes suggest that CPU significantly decreases RETBs across several data quantiles in our sample nations. In addition, the outcomes underscore that the connections between our variables differ among nations. These outcomes highlight the significance of policymakers implementing thorough appraisals and skillfully governing plans relevant to CPU and RETBs.

Global chessboard: Analyzing how geopolitical risk shapes renewable energy technology investments.

The allocation of budgets for renewable energy (RE) technology is significantly influenced by geopolitical risks (GPRs), reflecting the intricate interplay among global political dynamics, social media narratives, and the strategic investment decisions essential for advancing sustainable energy solutions. Against the backdrop of increasing worldwide initiatives to transition to RE sources, it is crucial to understand how GPR affects funding allocations, informing policy decisions, and fostering international collaboration to pursue sustainable energy solutions. Existing work probes the nonlinear effect of GPR on RE technology budgets (RTB) within the top 10 economies characterized by substantial research and development investments in RE (China, USA, Germany, Japan, France, South Korea, India, the United Kingdom, Australia, and Italy). Past research largely focused on panel data techniques to delve the interconnection between GPR and RE technology, overlooking the distinctive characteristics of individual economies. Contrarily, existing investigation implements the "Quantile-on-Quantile" tool to explore this association on an economy-particular basis, enhancing the precision of our analysis and offering both a comprehensive global perspective and nuanced perceptions for entire countries. The findings manifest a significant reduction in funding for RE technology associated with GPR across various quantile levels in the chosen economies. The disparities in results spotlight the necessity for policymakers to perform thorough assessments and carry out competent strategies to address the variations in GPR and RTB.

Innovative Adsorbents for Pollutant Removal: Exploring the Latest Research and Applications.

The growing presence of diverse pollutants, including heavy metals, organic compounds, pharmaceuticals, and emerging contaminants, poses significant environmental and health risks. Traditional methods for pollutant removal often face limitations in efficiency, selectivity, and sustainability. This review provides a comprehensive analysis of recent advancements in innovative adsorbents designed to address these challenges. It explores a wide array of non-conventional adsorbent materials, such as nanocellulose, metal-organic frameworks (MOFs), graphene-based composites, and biochar, emphasizing their sources, structural characteristics, and unique adsorption mechanisms. The review discusses adsorption processes, including the basic principles, kinetics, isotherms, and the factors influencing adsorption efficiency. It highlights the superior performance of these materials in removing specific pollutants across various environmental settings. The practical applications of these adsorbents are further explored through case studies in industrial settings, pilot studies, and field trials, showcasing their real-world effectiveness. Additionally, the review critically examines the economic considerations, technical challenges, and environmental impacts associated with these adsorbents, offering a balanced perspective on their viability and sustainability. The conclusion emphasizes future research directions, focusing on the development of scalable production methods, enhanced material stability, and sustainable regeneration techniques. This comprehensive assessment underscores the transformative potential of innovative adsorbents in pollutant remediation and their critical role in advancing environmental protection.

Computational fluid dynamics modeling of coronary artery blood flow using OpenFOAM: Validation with the food and drug administration benchmark nozzle model.

Cardiovascular disease (CVD), a global health concern, particularly coronary artery disease (CAD), poses a significant threat to well-being. Seeking safer and cost-effective diagnostic alternatives to invasive coronary angiography, noninvasive coronary computed tomography angiography (CCTA) gains prominence. This study employed OpenFOAM, an open-source Computational Fluid Dynamics (CFD) software, to analyze hemodynamic parameters in coronary arteries with serial stenoses. Patient-specific three-dimensional (3D) models from CCTA images offer insights into hemodynamic changes. OpenFOAM breaks away from traditional commercial software, validated against the FDA benchmark nozzle model for reliability. Applying this refined methodology to seventeen coronary arteries across nine patients, the study evaluates parameters like fractional flow reserve computed tomography simulation (FFRCTS), fluid velocity, and wall shear stress (WSS) over time. Findings include FFRCTS values exceeding 0.8 for grade 0 stenosis and falling below 0.5 for grade 5 stenosis. Central velocity remains nearly constant for grade 1 stenosis but increases 3.4-fold for grade 5 stenosis. This research innovates by utilizing OpenFOAM, departing from previous reliance on commercial software. Combining qualitative stenosis grading with quantitative FFRCTS and velocity measurements offers a more comprehensive assessment of coronary artery conditions. The study introduces 3D renderings of wall shear stress distribution across stenosis grades, providing an intuitive visualization of hemodynamic changes for valuable insights into coronary stenosis diagnosis.

Enhanced aqueous phosphorus removal and mechanism by water spinach (Ipomoea aquatica Forsk) pretreated with lanthanum nitrate.

Excess nutrients such as phosphate (PO43-) entering surface waters promote eutrophication, and phosphorous (P) removal is important to clear the water. Phytoremediation efforts have been used to improve water quality by varieties of P removal plants, such as water spinach (Ipomoea aquatica Forsk). Water spinach can reduce both internal and external resources of phosphorus from waterbody. The ion of lanthanum (La), one rare earth element (REE), is an immobilization substance for aqueous phosphate and also a fertilizer for plants. Therefore, lanthanum nitrate La (NO3)3 was used further to improve the phytoextraction of P from the polluted water. This study investigated the effects of La on the aqueous P removal by two genotypes of water spinach, green stem large leaves (GSLL) and green stem willow leaves (GSWL). The low concentration La (NO3)3 helped the plant to remove more phosphorous from eutrophic water, but La at high concentration lowered the removal of P. Under La (NO3)3 treatments, the optimum concentration for maximum P removal in GSLL is 3 mg/L, and for GSWL, it is 10 mg/L and P removal rates were enhanced to 95% and 96%, respectively. When the concentration of La (NO3)3 is 100 mg/L, the removal percentage of P was only 10% for both genotypes. The very high concentration of La will impose toxicity and even cause the death of the water spinach and produce secondary pollution; for example, under some specific circumstances, the bond between lanthanum and nitrates dissociates into lanthanum ions (La3⁺) and nitrate ions (NO3⁻). If the concentration is high, then it accumulates in the aquatic water organisms and plants and causes toxicity in their bodies. If humans eat up these plants and fish, it causes toxic effects in humans. The La (NO3)3 positively affects different parameters of plants. La (NO3)3 increases the growth, pigments, enzyme activity, and malondialdehyde (MDA) of plants which were also discussed in this study. The biological mechanism should be responsible for the enhanced aqueous phosphorus removal by water spinach using lanthanum nitrate.

Association of GRK5 variant rs10886471 with the therapeutic effect of repaglinide in patients of type 2 diabetes mellitus in Peshawar, Pakistan.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a rising global prevalence. The primary objective of this study was to explore the relationship between the GRK5 variant (rs10886471) and the therapeutic effect of repaglinide in patients of T2DM in Peshawar, Pakistan. A quasi-experimental study was designed. The study group consisted of patients with Type 2 Diabetes Mellitus (T2DM) categorized into responders and non-responders based on their HbA1c level reduction in response to repaglinide treatment. After ethical approval, and consent from the participants, sociodemographic and clinical data was collected from 60 T2DM patients. Blood samples were collected followed by DNA extraction and quantification with UV-Vis Spectroscopy. Genotyping for the GRK5 variant rs10886471 was done using the PCR-based method. Among socio-demographic factors family history and BMI showed significant association (P<0.05) with the therapeutic response to repaglinide. The Statistical analyses, including chi-square tests and logistic regression of GRK5 variant rs10886471 exhibited a significant association with the therapeutic response. Variant allele exhibited significant association (OR: 1.2, p=0.049) with the therapeutic response to repaglinide. The study demonstrated a significant relationship between the GRK5 variant (rs10886471) and the therapeutic response to repaglinide in patients of T2DM of Peshawar, Pakistan.

Combined application of hot water treatment and eucalyptus leaf extract postpones senescence in harvested green chilies by conserving their antioxidants: a sustainable approach.

BACKGROUND: Green chili is the predominant vegetable in tropical and subtropical regions with high economic value. However, after harvest, it exhibits vigorous metabolic activities due to the high moisture level, leading to a reduction in bioactive compounds and hence reduced shelf life and nutritional quality. Low temperature storage results in the onset of chilling injury symptoms. Therefore, developing techniques to increase the shelf life of green chilies and safeguard their nutritional value has become a serious concern for researchers. In this regard, an experiment was conducted to evaluate the impact of the alone or combined application of hot water treatment (HWT) (45 °C for 15 min) and eucalyptus leaf extract (ELE) (30%) on 'Golden Hot' chilies in comparison to the control. After treatment, chilies were stored at 20 ± 1.5 °C for 20 days. RESULTS: HWT + ELE-treated chilies had a significant reduction in fruit weight loss (14.6%), fungal decay index (35%), red chili percentage (41.2%), soluble solid content (42.9%), ripening index (48.9%), and reactive oxygen species production like H2O2 (55.1%) and O-2 (46.5%) during shelf in comparison to control, followed by the alone application of HWT and ELE. Furthermore, the combined use of HWT and ELE effectively improved the antioxidative properties of stored chilies including DPPH radical scavenging activities (54.6%), ascorbic acid content (28.4%), phenolic content (31.8%), as well as the enzyme activities of POD (103%), CAT (128%), SOD (26.5%), and APX (43.8%) in comparison to the control. Additionally, the green chilies underwent HWT + ELE treatment also exhibited higher chlorophyll levels (100%) and general appearance (79.6%) with reduced anthocyanin content (40.8%) and wrinkling (43%), leading to a higher marketable fruit (41.3%) than the control. CONCLUSION: The pre-storage application of HWT and ELE could be used as an antimicrobial, non-chemical, non-toxic, and eco-friendly treatment for preserving the postharvest quality of green chilies at ambient temperature (20 ± 1.5 °C).

Himalayan mountains imposing a barrier on gene flow of wheat yellow rust pathogen in the bordering regions of Pakistan and China.

The wheat yellow rust pathogen has been shown to be diverse and potentially originated in the Himalayan region. Although Himalayan populations of Pakistan, Nepal and Bhutan have been previously compared, little is known about the relative divergence and diversity in Puccinia striiformis populations in the bordering regions of Pakistan and China. To assess the relative diversity and divergence in these regions of Pakistan (Gilgit-Baltistan, Hazara and Azad Jammu Kashmir) and China (Xinjiang, Qinghai, Tibet, Sichuan, Guizhou and Yunnan), a total of 1245 samples were genotyped using 17 microsatellite SSR markers. A clear divergence was observed between the bordering regions of Pakistan and China (FST = 0.28) without any resampling of genetic groups and multilocus genotypes across two sides of the Himalayan mountains. The closest subpopulations across the two countries were Xinjiang and Gilgit-Baltistan (Nei's distance = 0.147), which were close geographically. A very high diversity and recombinant population structure was observed in both populations, though slightly higher in China (Genotypic diversity = 0.970; r¯d = 0.000) than in Pakistan (Genotypic diversity = 0.902; r¯d = 0.065). The distribution of genetic groups and resampling of MLGs revealed more gene flow across Yunnan, Guizhou and Sichuan regions in China, while between Hazara and Azad-Jammu Kashmir in Pakistan. The lack of gene flow between Pakistan and China populations is due to geographical barriers and a large patch of land without wheat. The information on the relative diversity and divergence in different geographical zones of the pathogen center of diversity and neighboring region should be considered in resistant wheat deployment while considering the invasion potential of the pathogen at regional and global contexts.

Evolution of the rice blast pathogen on spatially structured rice landraces maintains multiple generalist fungal lineages.

Traditional agrosystems, where humans, crops and microbes have coevolved over long periods, can serve as models to understand the ecoevolutionary determinants of disease dynamics and help the engineering of durably resistant agrosystems. Here, we investigated the genetic and phenotypic relationship between rice (Oryza sativa) landraces and their rice blast pathogen (Pyricularia oryzae) in the traditional Yuanyang terraces of flooded rice paddies in China, where rice landraces have been grown and bred over centuries without significant disease outbreaks. Analyses of genetic subdivision revealed that indica rice plants clustered according to landrace names. Three new diverse lineages of rice blast specific to the Yuanyang terraces coexisted with lineages previously detected at the worldwide scale. Population subdivision in the pathogen population did not mirror pattern of population subdivision in the host. Measuring the pathogenicity of rice blast isolates on landraces revealed generalist life history traits. Our results suggest that the implementation of disease control strategies based on the emergence or maintenance of a generalist lifestyle in pathogens may sustainably reduce the burden of disease in crops.

Plain language summary of the HIMALAYA study: tremelimumab and durvalumab for unresectable hepatocellular carcinoma (liver cancer).

WHAT IS THIS SUMMARY ABOUT?: This is a summary of results from a phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose of a medication called tremelimumab combined with multiple doses of a medication called durvalumab (the STRIDE regimen) or multiple doses of durvalumab alone. These treatments were compared with a medication called sorafenib in participants with unresectable hepatocellular carcinoma (HCC). HCC is a type of liver cancer that is difficult to treat because it is often diagnosed when it is unresectable, meaning it can no longer be removed with surgery. Sorafenib has been the main treatment for unresectable HCC since 2007. However, people who take sorafenib may experience side effects that can reduce their quality of life, so alternative medicines are being trialed. Tremelimumab and durvalumab are types of drugs called immunotherapies, and they both work in different ways to help the body's immune system fight cancer. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took STRIDE lived longer than participants who took sorafenib, whilst participants who took durvalumab alone lived a similar length of time as participants who took sorafenib. Participants who took STRIDE or durvalumab had a lower relative risk of experiencing worsening in their quality of life than participants who took sorafenib. The side effects that participants who received STRIDE or durvalumab experienced were expected for these types of treatments and could mostly be managed. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, STRIDE is more effective than sorafenib for people with unresectable HCC.

Revealing the energy paradox: Assessing the asymmetric impact of pandemic uncertainty on consumption of renewable and nonrenewable energy.

Uncertainties have grown around the world during the last few decades. Pandemic uncertainty has a substantial impact on economic activities, which may have a big influence on energy consumption. The goal of this investigation is to appraise the asymmetric influence of pandemic uncertainty on nonrenewable and renewable energy consumption in the top 10 energy consumer economies of the European Union (Germany, Poland, Spain, Netherlands, France, Italy, Belgium, Sweden, Czech Republic, and Finland). Previously, panel data approaches were utilized to obtain reliable outcomes on the pandemic-energy consumption nexus, regardless of the fact that various nations did not autonomously exhibit similar relationship. This investigation, on the other hand, implements a special technique "Quantile-on-Quantile" that supports us to appraise time-series interdependence in each economy by providing international yet nation-specific perceptions of the connection among the variables. Estimates show that pandemic uncertainty reduces both nonrenewable and renewable energy consumption in most selected nations at stated quantiles of the data distribution. Nonrenewable energy consumption is much more influenced by pandemic uncertainty than renewable energy consumption. Furthermore, the rank of asymmetries across our variables differentiates by the economy, emphasizing the need for decisionmakers to pay much attention to pandemics-related uncertainty and the energy sector.

Recent Advances in Smart Epidural Spinal Needles.

Lumbar puncture is a minimally invasive procedure that utilizes a spinal needle to puncture the lumbar epidural space to take a sample from the cerebrospinal fluid or inject drugs for diagnostic and therapeutic purposes. Physicians rely on their expertise to localize epidural space. Due to its critical procedure, the failure rate can reach up to 28%. Hence, a high level of experience and caution is required to correctly insert the needle without puncturing the dura mater, which is a fibrous layer protecting the spinal cord. Failure of spinal anesthesia is, in some cases, related to faulty needle placement techniques since it is blindly inserted. Therefore, advanced techniques for localization of the epidural space are essential to avoid any possible side effects. As for epidural space localization, various ideas were carried out over recent years to provide accurate identification of the epidural space. Subsequently, several methodologies based on mechanical and optical schemes have been proposed. Several research groups worked from different aspects of the problem, namely, the clinical and engineering sides. Hence, the main goal of this paper is to review this research with the aim of remedying the gap between the clinical side of the problem and the engineering side by examining the main techniques in building sensors for such purposes. This manuscript provides an understanding of the clinical needs of spinal needles from an anatomical point of view. Most importantly, it discusses the mechanical and optical approaches in designing and building sensors to guide spinal needles. Finally, the standards that must be followed in building smart spinal needles for approval procedures are also presented, along with some insight into future directions.