The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.

SARS-CoV-2 infection can cause severe pneumonia, wherein exacerbated inflammation plays a major role. This is reminiscent of the process commonly termed cytokine storm, a condition dependent on a disproportionated production of cytokines. This state involves the activation of the innate immune response by viral patterns and coincides with the biosynthesis of the biomass required for viral replication, which may overwhelm the capacity of the endoplasmic reticulum and drive the unfolded protein response (UPR). The UPR is a signal transduction pathway composed of three branches that is initiated by a set of sensors: inositol-requiring protein 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6). These sensors control adaptive processes, including the transcriptional regulation of proinflammatory cytokines. Based on this background, the role of the UPR in SARS-CoV-2 replication and the ensuing inflammatory response was investigated using in vivo and in vitro models of infection. Mice and Syrian hamsters infected with SARS-CoV-2 showed a sole activation of the Ire1α-Xbp1 arm of the UPR associated with a robust production of proinflammatory cytokines. Human lung epithelial cells showed the dependence of viral replication on the expression of UPR-target proteins branching on the IRE1α-XBP1 arm and to a lower extent on the PERK route. Likewise, activation of the IRE1α-XBP1 branch by Spike (S) proteins from different variants of concern was a uniform finding. These results show that the IRE1α-XBP1 system enhances viral replication and cytokine expression and may represent a potential therapeutic target in SARS-CoV-2 severe pneumonia.

Baseline findings of a multicentric ambispective cohort study (2021-2022) among hospitalised mucormycosis patients in India.

In India, the incidence of mucormycosis reached high levels during 2021-2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March-July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease's clinical progression and help frame standard treatment guidelines.

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats.

Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal (GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.

The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice.

Objectives: Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute to the emergence of variants with altered pathogenicity due to persistent infection. This study investigated the impact of immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice and the effectiveness of antiviral treatments in this context. Methods: Mice were immunosuppressed using cyclophosphamide and infected with a B lineage of SARS-CoV-2. Molnupiravir and nirmatrelvir, alone and in combination, were administered and viral load and viral sequence diversity was assessed. Results: Treatment of infected but immune compromised mice with both compounds either singly or in combination resulted in decreased viral loads and pathological changes compared to untreated animals. Treatment also abrogated infection of neuronal tissue. However, no consistent changes in the viral consensus sequence were observed, except for the emergence of the S:H655Y mutation. Molnupiravir, but not nirmatrelvir or immunosuppression alone, increased the transition/transversion (Ts/Tv) ratio, representative of A>G and C>U mutations and this increase was not altered by the co-administration of nirmatrelvir with molnupiravir.Notably, immunosuppression itself did not appear to promote the emergence of mutational characteristic of variants of concern (VOCs). Conclusions: Further investigations are warranted to fully understand the role of immunocompromised individuals in VOC development and to inform optimised public health strategies. It is more likely that immunodeficiency promotes viral persistence but does not necessarily lead to substantial consensus-level changes in the absence of antiviral selection pressure. Consistent with mechanisms of action, molnupiravir showed a stronger mutagenic effect than nirmatrelvir in this model.

A Prospective Study to Evaluate the Role of Combined Diagnostic Laparoscopy and Hysteroscopy in the Management of Female Infertility.

Introduction Infertility affects approximately 10-15% of couples worldwide. Hysteroscopy and laparoscopy are two newer modalities available for the evaluation of infertility and are complementary rather than mutually exclusive. Each provides useful information that the other may not have and each has its advantages. Materials and methods A total of 75 patients of female infertility (study group) in the age group of 18-40 years from the Outpatient Department (OPD) were recruited. Infertility was defined as one year of unprotected intercourse without pregnancy. Hysteroscopy and laparoscopy were carried out in each patient at the follicular phase of the menstrual cycle. Hysteroscopic findings were compared with laparoscopic findings for uterine and tubal pathology. Hysteroscopy as a procedure was also compared with laparoscopy as a one-step procedure for diagnostic accuracy in investigating a case of female infertility. The data was analyzed by Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 29.0, Armonk, NY). Observations and results In our study, out of a total of 75 cases evaluated for infertility, primary infertility patients were 48 (64%) and secondary infertility patients were 27 (36%). In our study, both tubes were patent on chromopertubation in primary infertility (PI) vs secondary infertility (SI) in 49.33% vs 21.33% of total cases. Both tubes were blocked in PI vs SI in 9.33% vs 8% of total cases. In our study, 20 patients (26.66%) underwent hysteroscopic intervention. Adhesiolysis was the commonest procedure required in seven (9.33%) followed by hysteroscopic cannulation in six (8%). In our study, a total of 30 procedures were performed in 20 patients during laparoscopy. The most common procedure required was ovarian drilling in 22.66% (17/75) followed by surgery for endometriosis in 10.66% (8/75). Adhesiolysis was required in 5/75 (6.66%). Both laparoscopy and hysteroscopy were normal in 44/75 cases for uterine findings. Conclusion Thus, hysterolaparoscopy as "one step" had various advantages in our study, more accuracy in the findings and therapeutic intervention in the same sitting reducing the cost. The addition of hysteroscopy to laparoscopy is invaluable in the infertility workup as it has a definite edge in the detection of uterine pathology, as well as being therapeutic at the same time. More accuracy in the diagnostic findings and therapeutic intervention in the same setting will help in reducing the time and cost of treatment.

Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression.

Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen.

GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30-3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43-5.87, P = 0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

A Survey of Xylella fastidiosa in the U.S. State of Virginia Reveals Wide Distribution of Both Subspecies fastidiosa and multiplex in Grapevine.

Global travel and trade in combination with climate change are expanding the geographic distribution of plant pathogens. The bacterium Xylella fastidiosa is a prime example. Native to the Americas, it has spread to Europe, Asia, and the Middle East. To assess the risk that pathogen introductions pose to crops in newly invaded areas, it is key to survey their diversity, host range, and disease incidence in relation to climatic conditions where they are already present. We performed a survey of X. fastidiosa in grapevine in Virginia using a combination of quantitative PCR, multilocus sequencing, and metagenomics. We also analyzed samples from deciduous trees with leaf scorch symptoms. X. fastidiosa subspecies fastidiosa was identified in grapevines in all regions of the state, even in Northern Virginia, where the temperature was below -9°C for 10 days per year on average in the years preceding sampling. Unexpectedly, we also found for the first time grapevine samples infected with X. fastidiosa subspecies multiplex (Xfm). The Xfm lineage found in grapevines had been previously isolated from blueberries in the Southeastern United States and was distinct from that found in deciduous trees in Virginia. The obtained results will be important for risk assessment of X. fastidiosa introductions in other parts of the world.

Bioanalytical Method Development and Validation of Doxorubicin and Lapatinib in Rat Plasma Using UHPLC-HESI-LTQ-MS.

Cancer is considered a silent killer. The complexity of cancer makes it earn that title. So far there are only a few approaches to treat cancer. Among them, chemotherapy is considered the best approach. Many chemotherapeutical compounds are commercially available in the market. Among them, doxorubicin (DOX) and lapatinib (LAP) are considered blockbuster molecules. However, DOX suffers from poor bioavailability and exhibits cardiotoxicity. Interestingly, a fixed dose combination of DOX and LAP significantly decreases the cardiotoxic effect of DOX. To enhance the oral bioavailability of DOX and to avail the synergistic effect of LAP, many formulations have been made. To quantify both compounds in any formulation or biological matrix, an Liquid chromatography-Mass Spectrometry (LC-MS) method is required. In this present study, a simple and rapid Ultra High-Performance Liquid Chromatography - Heated Electron Spray Ionization - Mass Spectrometry (UHPLC-HESI-MS) bioanalytical method was developed. The developed method was validated as per the regulatory guidelines. The validated bioanalytical method had a lower limit of quantification of 0.75 ng. A simple protein precipitation technique was optimized to extract the compounds from the rat plasma. All the validation parameters were found to be within the limits as per the regulatory guidelines. A novel and rapid analytical method was successfully developed and validated. This developed method can be used to quantify the DOX and LAP in any formulation and biological matrix.

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.

FLAgellum Member 8 modulates extravascular distribution of African trypanosomes.

In the mammalian host, the biology of tissue-dwelling Trypanosoma brucei parasites is not completely understood, especially the mechanisms involved in their extravascular colonization. The trypanosome flagellum is an essential organelle in multiple aspects of the parasites' development. The flagellar protein termed FLAgellar Member 8 (FLAM8) acts as a docking platform for a pool of cyclic AMP response protein 3 (CARP3) that is involved in signaling. FLAM8 exhibits a stage-specific distribution suggesting specific functions in the mammalian and vector stages of the parasite. Analyses of knockdown and knockout trypanosomes in their mammalian forms demonstrated that FLAM8 is not essential in vitro for survival, growth, motility and stumpy differentiation. Functional investigations in experimental infections showed that FLAM8-deprived trypanosomes can establish and maintain an infection in the blood circulation and differentiate into insect transmissible forms. However, quantitative bioluminescence imaging and gene expression analysis revealed that FLAM8-null parasites exhibit a significantly impaired dissemination in the extravascular compartment, that is restored by the addition of a single rescue copy of FLAM8. In vitro trans-endothelial migration assays revealed significant defects in trypanosomes lacking FLAM8. FLAM8 is the first flagellar component shown to modulate T. brucei distribution in the host tissues, possibly through sensing functions, contributing to the maintenance of extravascular parasite populations in mammalian anatomical niches, especially in the skin.

Anaesthetic Management and Physiologic Effects of Pneumoperitoneum in Patients With Chronic Obstructive Pulmonary Disease Undergoing Laparoscopic Cholecystectomy.

OBJECTIVE: This study aimed to assess the physiological changes and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) undergoing laparoscopic cholecystectomy. METHODS: This prospective cohort study included 50 patients of the American Society of Anesthesiology (ASA) physical status I and II with mild to moderate COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-II) scheduled for laparoscopic cholecystectomy. We monitored heart rate, mean arterial pressure, end-tidal carbon dioxide (EtCO2), arterial carbon dioxide (PaCO2), and bicarbonate (HCO3) levels at baseline, 30 minutes after induction or 15 minutes post-insufflation, 15 minutes post-deflation, and 60 minutes post-operative. Perioperative complications and post-operative recovery characteristics were also observed. Descriptive statistics were used to summarise the demographic and clinical characteristics of the patients. The correlation between HCO3 and EtCO2 was plotted on a scatterplot, and Pearson's correlation 'r' was calculated. The changes in physiological parameters over time were analysed using a paired t-test. A p-value of less than 0.05 is considered statistically significant. RESULTS: We observed a statistically significant but transient increase in heart rate, mean arterial pressure, and EtCO2 at 30 minutes after induction or 15 minutes post-insufflation, which returned to baseline levels within 15 minutes of deflation. Similarly, arterial CO2 and bicarbonate levels were also significantly increased at 15 minutes post-insufflation, yet remained within the normal physiological range. The study reported no serious perioperative complications, and all patients had an uneventful recovery. CONCLUSION: While patients with mild to moderate COPD can experience transient physiological changes during laparoscopic cholecystectomy, these changes are generally well-tolerated and not associated with adverse clinical outcomes. Therefore, laparoscopic cholecystectomy can be considered a safe procedure in these patients. Future research should focus on the implications and safety of this procedure in patients with severe COPD.

The Effect of Increasing Bath Temperature on the Contractile Responses of the Large Gut in Adult and Neonate Rats.

Introduction Earlier reports on the effect of temperature on gut motility concentrated on experiments conducted on the small intestines of adult animals. The effect of temperature on the large intestine, particularly in neonates, warrants further investigation. The current study investigated the effect of a temperature increase and its mechanism in the colon and rectum of neonate and adult rats. Methods and materials In an organ bath preparation, segments from the colon and rectum were subjected to increasing bath temperatures (37°C-40°C). In other groups, pretreatment with capsazepine (1 µM) and Nω-nitro-l-arginine methyl ester (L-NAME) (100 µM) was done, in different groups, to assess their impact on temperature-induced contractile response. Results Increasing the bath temperature significantly reduced the contractile tension in the colon and rectum. When L-NAME (100 µM)-pretreated segments of the colon and rectum were subjected to different bath temperatures, the contractile tension increased compared to the contractile tension at different bath temperatures without any drug. Capsazepine (1 µM) pretreatment, on the other hand, enhanced the decrease in the contractile tension in the colon and rectum of adult rats compared to the contractile tension produced at different bath temperatures without any drug, while in neonates, capsazepine (1 µM) pretreatment caused a rise in the contractile tension in the rectum with no effect in the colon. Increased bath temperature from 37°C to 40°C increased the contractile frequency in the colon and rectum in both adult and neonate rats. Pretreatment with L-NAME (100 µM) and capsazepine (1 µM) in adults and L-NAME (100 µM) in neonates caused an increase in the contractile frequency in both the colon and rectum; on the other hand, capsazepine pretreatment did not affect the contractile frequency in the colon and rectum of neonate rats compared to the contractile frequency produced at different bath temperatures without any drug. Conclusion The contractile response of rats' large intestines, colon, and rectum to increasing temperatures may involve nitric oxide (NO)-mediated and transient receptor potential vanilloid-1 (TRPV1)-mediated mechanisms. The effects of capsazepine on the colon and rectum of adults and neonates differ, possibly due to the TRPV1-mediated mechanism not developing properly in the neonate and developing later in adulthood.

Genomic delineation and description of species and within-species lineages in the genus Pantoea.

As the name of the genus Pantoea ("of all sorts and sources") suggests, this genus includes bacteria with a wide range of provenances, including plants, animals, soils, components of the water cycle, and humans. Some members of the genus are pathogenic to plants, and some are suspected to be opportunistic human pathogens; while others are used as microbial pesticides or show promise in biotechnological applications. During its taxonomic history, the genus and its species have seen many revisions. However, evolutionary and comparative genomics studies have started to provide a solid foundation for a more stable taxonomy. To move further toward this goal, we have built a 2,509-gene core genome tree of 437 public genome sequences representing the currently known diversity of the genus Pantoea. Clades were evaluated for being evolutionarily and ecologically significant by determining bootstrap support, gene content differences, and recent recombination events. These results were then integrated with genome metadata, published literature, descriptions of named species with standing in nomenclature, and circumscriptions of yet-unnamed species clusters, 15 of which we assigned names under the nascent SeqCode. Finally, genome-based circumscriptions and descriptions of each species and each significant genetic lineage within species were uploaded to the LINbase Web server so that newly sequenced genomes of isolates belonging to any of these groups could be precisely and accurately identified.

Comparison of acceptability & efficacy of thermal ablation (thermocoagulation) & cryotherapy in VIA positive cervical lesions: A pilot study.

BACKGROUND OBJECTIVES: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy. METHODS: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months. RESULTS: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant). INTERPRETATION CONCLUSIONS: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.

De novo transcriptome profiling and development of novel secondary metabolites based genic SSRs in medicinal plant Phyllanthus emblica L. (Aonla).

Phyllanthus emblica (Aonla, Indian Gooseberry) is known to have various medicinal properties, but studies to understand its genetic structure are limited. Among the various secondary metabolites, ascorbic acid, flavonoids, terpenoids, phenols and tannins possess great potential for its pharmacological applications. Keeping this consideration, we assembled the transcriptome using the Illumina RNASeq500 platform, generating 39,933,248 high-quality paired-end reads assembled into 1,26,606 transcripts. A total of 87,771 unigenes were recovered after isoforms and unambiguous sequences deletion. Functional annotation of 43,377 coding sequences against the NCBI non-redundant (Nr) database search using BlastX yielded 38,692 sequences containing blast hits and found 4685 coding sequences to be unique. The transcript showed maximum similarity to Hevea brasilensis (16%), followed by to Jatropha curcas (12%). Considering key genes involved in the biosynthesis of flavonoids and various classes of terpenoid compounds, thirty EST-SSR primer sequences were designed based on transcriptomic data. Of which, 12 were found to be highly polymorphic with an average of 86.38%. The average value for marker index (MI), effective multiplicity ratio (EMR), resolution power (Rp) and polymorphic information content (PIC) was 7.20, 8.34, 8.64 and 0.80, respectively. Thus, from this study, we developed newly EST-SSRs linked to important genes involved in the secondary metabolites biosynthesis that will be serving as an invaluable genetic resource for crop improvement including the selection of elite genotypes in P. emblica and its closely related Phyllanthaceae species.

Physiological and omics-based insights for underpinning the molecular regulation of secondary metabolite production in medicinal plants: UV stress resilience.

Despite complex phytoconstituents, the commercial potential of medicinal plants under ultraviolet (UV) stress environment hasn't been fully comprehended. Due to sessile nature, these plants are constantly exposed to damaging radiation, which disturbs their natural physiological and biochemical processes. To combat with UV stress, plants synthesized several small organic molecules (natural products of low molecular mass like alkaloids, terpenoids, flavonoids and phenolics, etc.) known as plant secondary metabolites (PSMs) that come into play to counteract the adverse effect of stress. Plants adapted a stress response by organizing the expression of several genes, enzymes, transcription factors, and proteins involved in the synthesis of chemical substances and by making the signaling cascade (a series of chemical reactions induced by a stimulus within a biological cell) flexible to boost the defensive response. To neutralize UV exposure, secondary metabolites and their signaling network regulate cellular processes at the molecular level. Conventional breeding methods are time-consuming and difficult to reveal the molecular pattern of the stress tolerance medicinal plants. Acquiring in-depth knowledge of the molecular drivers behind the defensive mechanism of medicinal plants against UV radiation would yield advantages (economical and biological) that will bring prosperity to the burgeoning world's population. Thus, this review article emphasized the comprehensive information and clues to identify several potential genes, transcription factors (TFs), proteins, biosynthetic pathways, and biological networks which are involved in resilience mechanism under UV stress in medicinal plants of high-altitudes.

Observation of a quality improvement initiative to contextually adapt and use Robson classification in real time to collect data around CS delivery and to develop strategies to reduce CS rate.

The rising trend in caesarean section (CS) rate is a global concern and, in this hospital too, it rose from 21.5% in 2010 to 32.6% in 2018. The team followed the point of care quality improvement methodology and conducted a series of Plan-Do-Study-Act cycles to contextually modify and adapt Robson classification into the existing workflow to improve the process of documentation and data collection for CS in the first 6 months (January 2019-June 2019) and then to use these data to develop strategies to reduce CS rate below 30% in the next 18 months.To evaluate the impact of developed strategies, the team plotted the data on Statistical Process Control (XmR) chart. The baseline mean CS rate was 32.6%. The team observed a shift in the CS rate data twice, between April 2020 and December 2020 and between August 2021 and February 2021 with the mean 27.8% and 28.9%, respectively. October 2021 onwards, the team also observed a sustained reduction in the CS rate in women undergoing CS who had one previous CS. The mean CS rate reduced from 94% to 86%.The reductions in the CS rate were not sustained and followed by an increase again. The project highlighted the complexity of the factors related to CS delivery and the multidimensional barriers of sustaining the reduction in the CS rate. This is a well-sustained ongoing QI intervention and the team is further working on identifying the underlying factors to improve the efficacy of the interventions to sustain the reduction in the CS rate.This hospital represents the general population of North India seeking care in public healthcare facilities. Therefore, despite being a single-centre study, the population served and interpretations drawn from this study are generalisable to other hospitals with similar settings.

Drought and heat stress mediated activation of lipid signaling in plants: a critical review.

Lipids are a principal component of plasma membrane, acting as a protective barrier between the cell and its surroundings. Abiotic stresses such as drought and temperature induce various lipid-dependent signaling responses, and the membrane lipids respond differently to environmental challenges. Recent studies have revealed that lipids serve as signal mediators forreducing stress responses in plant cells and activating defense systems. Signaling lipids, such as phosphatidic acid, phosphoinositides, sphingolipids, lysophospholipids, oxylipins, and N-acylethanolamines, are generated in response to stress. Membrane lipids are essential for maintaining the lamellar stack of chloroplasts and stabilizing chloroplast membranes under stress. However, the effects of lipid signaling targets in plants are not fully understood. This review focuses on the synthesis of various signaling lipids and their roles in abiotic stress tolerance responses, providing an essential perspective for further investigation into the interactions between plant lipids and abiotic stress.