The genomic origins of the Bronze Age Tarim Basin mummies.

The identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000-2800 BC from the Dzungarian Basin and 13 individuals dating to around 2100-1700 BC from the Tarim Basin, representing the earliest yet discovered human remains from North and South Xinjiang, respectively. We find that the Early Bronze Age Dzungarian individuals exhibit a predominantly Afanasievo ancestry with an additional local contribution, and the Early-Middle Bronze Age Tarim individuals contain only a local ancestry. The Tarim individuals from the site of Xiaohe further exhibit strong evidence of milk proteins in their dental calculus, indicating a reliance on dairy pastoralism at the site since its founding. Our results do not support previous hypotheses for the origin of the Tarim mummies, who were argued to be Proto-Tocharian-speaking pastoralists descended from the Afanasievo1,2 or to have originated among the Bactria-Margiana Archaeological Complex3 or Inner Asian Mountain Corridor cultures4. Instead, although Tocharian may have been plausibly introduced to the Dzungarian Basin by Afanasievo migrants during the Early Bronze Age, we find that the earliest Tarim Basin cultures appear to have arisen from a genetically isolated local population that adopted neighbouring pastoralist and agriculturalist practices, which allowed them to settle and thrive along the shifting riverine oases of the Taklamakan Desert.

Thermo-Chemical Cues-Mediated Strategy to Control Peptide Self-Assembly and Charge Transfer Complexation.

Peptide amphiphiles (PAs) are known for their remarkable ability to undergo molecular self-assembly, a process that is highly responsive to the local microenvironment. Herein, we design a pyrene tethered peptide amphiphile Py-VFFAKK, 1 that exhibits pathway-driven self-assembly from metastable nanoparticles to kinetically controlled nanofibers and thermodynamically stable twisted bundles upon modulations in pH, temperature, and chemical cues. The presence of the pyrene moiety ensures donation of the electron to an electron acceptor, namely, 7,7,8,8-tetracyanoquinodimethane (TCNQ), to form a supramolecular charge transfer complex in aqueous solution that was studied in detail with microscopic and spectroscopic techniques. Excitation of the donor species in its excimer state facilitates electron donation to the acceptor moiety, paving away a long-lived charge-separated state that persists for over a nanosecond, as ascertained through transient absorption spectroscopy. Finally, the self-assembled charge transfer complex is explored toward antimicrobial properties with Escherichia coli while maintaining biocompatibility toward L929 mice fibroblast cells.

Photoswitching of arylazopyrazoles upon S1 (nπ*) excitation studied by transient absorption spectroscopy and ab initio molecular dynamics.

Arylazopyrazoles (AAPs) are an important class of molecular photoswitches with high photostationary states (PSS) and long thermal lifetimes. The ultrafast photoisomerization of four water-soluble arylazopyrazoles, all of them featuring an ortho-dimethylated pyrazole ring, is studied by narrowband femtosecond transient absorption spectroscopy and ab initio molecular dynamics simulations. Upon S1 (nπ*) photoexcitation of the planar E-isomers (E-AAPs), excited-state bi-exponential decays with time constants τ1 in the 220-440 fs range and τ2 in the 1.4-1.8 ps range are observed, comparable to those reported for azobenzene (AB). This is indicative of the same photoisomerization mechanism as has been reported for ABs. In contrast to the planar E-AAPs, a twisted E-AAP with two methyl groups in ortho-position of the phenyl ring displays faster initial photoswitching with τ1 = 170 ± 10 fs and τ2 = 1.6 ± 0.1 ps. Our static DFT calculations and ab initio molecular dynamics simulations of E-AAPs on the S0 and S1 potential energy surfaces suggest that twisted E-isomer azo photoswitches exhibit faster initial photoisomerization dynamics out of the Franck-Condon region due to a weaker π-coordination of the central CNNC unit to the aromatic ligands.

Optical modeling and computational analysis of improved daylight collector geometry for a tubular skylight.

A carefully designed daylight collector for a tubular skylight is necessary to serve the occupants' illumination needs under the dynamic trajectory of the sun. This work simulated an improved configuration of a passive daylight collector comprising parabolic and conical reflectors in a modeled room using the lighting software tool TracePro. Results indicated that the lighting performance of the proposed design configuration was significantly enhanced under low altitude sun in comparison with conventional tubular skylights (with revolved parabolic and cylindrical reflectors) [Light. Res. Technol.52, 495 (2020)10.1177/1477153519872794] and hemispherical transparent dome as daylight collectors by more than ∼30%-40% and ∼110%-130%, respectively.

Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase.

The transition from growth to stationary phase is a natural response of bacteria to starvation and stress. When stress is alleviated and more favorable growth conditions return, bacteria resume proliferation without a significant loss in fitness. Although specific adaptations that enhance the persistence and survival of bacteria in stationary phase have been identified, mechanisms that help maintain the competitive fitness potential of nondividing bacterial populations have remained obscure. Here, we demonstrate that staphylococci that enter stationary phase following growth in media supplemented with excess glucose, undergo regulated cell death to maintain the competitive fitness potential of the population. Upon a decrease in extracellular pH, the acetate generated as a byproduct of glucose metabolism induces cytoplasmic acidification and extensive protein damage in nondividing cells. Although cell death ensues, it does not occur as a passive consequence of protein damage. Instead, we demonstrate that the expression and activity of the ClpXP protease is induced, resulting in the degeneration of cellular antioxidant capacity and, ultimately, cell death. Under these conditions, inactivation of either clpX or clpP resulted in the extended survival of unfit cells in stationary phase, but at the cost of maintaining population fitness. Finally, we show that cell death from antibiotics that interfere with bacterial protein synthesis can also be partly ascribed to the corresponding increase in clpP expression and activity. The functional conservation of ClpP in eukaryotes and bacteria suggests that ClpP-dependent cell death and fitness maintenance may be a widespread phenomenon in these domains of life.

Characterization of Complete Mitochondrial Genome of Badri Breed of Bos indicus (Bovidae: Bovinae): Selection Pressure and Comparative Analysis.

High-altitude mammals are often subject to specific environmental obstacles, which exert selective pressure on their physiological and morphological traits, hence driving their evolutionary processes. It is anticipated that these circumstances will lead to the adaptive evolution of protein-coding genes (PCGs) in the mitochondrial genome, which play a crucial role in the oxidative phosphorylation system. In this study, we have generated the complete mitochondrial genome of the Badri breed of Bos indicus inhabiting a high-altitude environment to test the signatures of adaptive evolution on PCGs and their phylogenetic relationships. The complete mitogenome of the Badri breed is 16,339 bp and most tRNAs showed typical clover-leaf secondary structure with a few exceptions, like trnS1 and trnS2 without DHU arm and trnK without DHU loop. Comparative analysis of PCGs indicated that cox1 is the most conserved, while atp6 is the most variable gene. Moreover, the ratios of non-synonymous to synonymous substitution rates indicated the purifying selection (Ka/Ks < 1) in the protein-coding genes that shape the diversity in mitogenome of Bos indicus. Furthermore, Branch-site model (BSM) suggested that cox1, cox2, nad3, nad4L, and nad6 underwent stronger purifying selection (ω < 1) than other PCGs in 15 breeds of 4 species, including Badri. BSM also detected 10 positive sites in PCGs and one in 13 PCGs concatenated dataset. Additional analyses in Datamonkey indicated 11 positive sites and 23 purifying sites in the concatenated dataset, a relaxation of selection strength in nad3, and no evidence of episodic diversifying selection in any PCGs. Phylogeny revealed the sister relationship of the Badri with other breeds of Bos indicus as well as Bos frontalis (Gayal-2). The mitogenome of the Badri breed is an important genomic resource for conservation genetics of this species and also contributes to the understanding of the adaptive evolution of mitochondrial protein coding genes.

Phyto-Fabrication of Moringa Oleifera Peel-Sourced Silver Nanoparticles: A Promising Approach for Combating Hepatic Cancer by Targeting Proinflammatory Cytokines and Mitigating Cytokine Storms.

Hepatocellular carcinoma (HCC) arises from precancerous nodules, leading to liver damage and inflammation, which triggers the release of proinflammatory cytokines. Dysregulation of these cytokines can escalate into a cytokine storm, causing severe organ damage. Interestingly, Moringa oleifera (M. oleifera) fruit peel, previously discarded as waste, contains an abundance of essential biomolecules and high nutritional value. This study focuses on the eco-friendly synthesis of silver nanoparticles infused with M. oleifera peel extract biomolecules and their impact on regulating proinflammatory cytokines, as well as their potential anticancer effects against Wistar rats. The freshly synthesized nanoformulation underwent comprehensive characterization, followed by antihepatic cancer evaluation using a diethyl nitrosamine-induced model (at a dose of 200 mg kg-1 BW). The study demonstrates a significant reduction in proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, interleukin-1ß, and nuclear factor kappa beta (NF-κB). Furthermore, it confirms that the newly biosynthesized silver nanoparticles exhibit additional potential against hepatic cancer due to their capped biomolecules.

Evaluating the fairness and accuracy of machine learning-based predictions of clinical outcomes after anatomic and reverse total shoulder arthroplasty.

BACKGROUND: Machine learning (ML)-based clinical decision support tools (CDSTs) make personalized predictions for different treatments; by comparing predictions of multiple treatments, these tools can be used to optimize decision making for a particular patient. However, CDST prediction accuracy varies for different patients and also for different treatment options. If these differences are sufficiently large and consistent for a particular subcohort of patients, then that bias may result in those patients not receiving a particular treatment. Such level of bias would deem the CDST "unfair." The purpose of this study is to evaluate the "fairness" of ML CDST-based clinical outcomes predictions after anatomic (aTSA) and reverse total shoulder arthroplasty (rTSA) for patients of different demographic attributes. METHODS: Clinical data from 8280 shoulder arthroplasty patients with 19,249 postoperative visits was used to evaluate the prediction fairness and accuracy associated with the following patient demographic attributes: ethnicity, sex, and age at the time of surgery. Performance of clinical outcome and range of motion regression predictions were quantified by the mean absolute error (MAE) and performance of minimal clinically important difference (MCID) and substantial clinical benefit classification predictions were quantified by accuracy, sensitivity, and the F1 score. Fairness of classification predictions leveraged the "four-fifths" legal guideline from the US Equal Employment Opportunity Commission and fairness of regression predictions leveraged established MCID thresholds associated with each outcome measure. RESULTS: For both aTSA and rTSA clinical outcome predictions, only minor differences in MAE were observed between patients of different ethnicity, sex, and age. Evaluation of prediction fairness demonstrated that 0 of 486 MCID (0%) and only 3 of 486 substantial clinical benefit (0.6%) classification predictions were outside the 20% fairness boundary and only 14 of 972 (1.4%) regression predictions were outside of the MCID fairness boundary. Hispanic and Black patients were more likely to have ML predictions out of fairness tolerance for aTSA and rTSA. Additionally, patients <60 years old were more likely to have ML predictions out of fairness tolerance for rTSA. No disparate predictions were identified for sex and no disparate regression predictions were observed for forward elevation, internal rotation score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score, or global shoulder function. CONCLUSION: The ML algorithms analyzed in this study accurately predict clinical outcomes after aTSA and rTSA for patients of different ethnicity, sex, and age, where only 1.4% of regression predictions and only 0.3% of classification predictions were out of fairness tolerance using the proposed fairness evaluation method and acceptance criteria. Future work is required to externally validate these ML algorithms to ensure they are equally accurate for all legally protected patient groups.

Microbial pigments: Sources, current status, future challenges in cosmetics and therapeutic applications.

Color serves as the initial attraction and offers a pleasing aspect. While synthetic colorants have been popular for many years, their adverse environmental and health effects cannot be overlooked. This necessitates the search for natural colorants, especially microbial colorants, which have proven and more effective. Pigment-producing microorganisms offer substantial benefits. Natural colors improve product marketability and bestow additional benefits, including antioxidant, antiaging, anticancer, antiviral, antimicrobial, and antitumor properties. This review covers the various types of microbial pigments, the methods to enhance their production, and their cosmetic and therapeutic applications. We also address the challenges faced during the commercial production of microbial pigments and propose potential solutions.

Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies.

Diabetes mellitus is a prevalent cause of mortality worldwide and can lead to several secondary issues, including DWs, which are caused by hyperglycemia, diabetic neuropathy, anemia, and ischemia. Roughly 15% of diabetic patient's experience complications related to DWs, with 25% at risk of lower limb amputations. A conventional management protocol is currently used for treating diabetic foot syndrome, which involves therapy using various substances, such as bFGF, pDGF, VEGF, EGF, IGF-I, TGF-ß, skin substitutes, cytokine stimulators, cytokine inhibitors, MMPs inhibitors, gene and stem cell therapies, ECM, and angiogenesis stimulators. The protocol also includes wound cleaning, laser therapy, antibiotics, skin substitutes, HOTC therapy, and removing dead tissue. It has been observed that treatment with numerous plants and their active constituents, including Globularia Arabica, Rhus coriaria L., Neolamarckia cadamba, Olea europaea, Salvia kronenburgii, Moringa oleifera, Syzygium aromaticum, Combretum molle, and Myrtus communis, has been found to promote wound healing, reduce inflammation, stimulate angiogenesis, and cytokines production, increase growth factors production, promote keratinocyte production, and encourage fibroblast proliferation. These therapies may also reduce the need for amputations. However, there is still limited information on how to prevent and manage DWs, and further research is needed to fully understand the role of alternative treatments in managing complications of DWs. The conventional management protocol for treating diabetic foot syndrome can be expensive and may cause adverse side effects. Alternative therapies, such as medicinal plants and green synthesis of nano-formulations, may provide efficient and affordable treatments for DWs.

Long-term Outcome of Coronavirus Disease-associated Mucormycosis: 1-year Follow-up Study from India.

IMPORTANCE: Invasive fungal infections have recently become a public health problem, particularly in India following the second wave of coronavirus disease 2019 (COVID-19). India harbors the world's largest population of patients suffering from diabetes. What prompted the sudden spike of mucormycosis infections in the COVID pandemic needs investigation. OBJECTIVE: To determine if COVID-19 infection prompted the spike in invasive fungal infections in diabetic population. To determine the long-term outcome of COVID-associated mucormycosis. To determine if COVID-19 infection causes diabetes mellitus transiently. DESIGN: The study was a prospective cohort study comprising patients suffering from mucormycosis. The study was planned from 20 May 2021, until 30 November 2022, to investigate the long-term follow-up (1 year) of mucormycosis patients. SETTING: The study setting was a referral hospital. PARTICIPANTS: All the consecutive patients admitted to this hospital for treatment of mucormycosis were included in the study who consented to it. Intervention(s) (for clinical trials) or exposure(s) (for observational studies): All patients suffering with mucormycosis underwent treatment at this hospital with surgery and injectable systemic antifungal drugs alongside diabetes management. MAIN OUTCOME(S) AND MEASURE(S): Primary outcome measurement was in the form of survival with cure of mucormycosis. Hypothesis being tested was formulated during data collection. RESULTS: The data of 98 participants was collected, but analysis was done after excluding the case of cutaneous mucormycosis (infant patient). Mean age for patients was 55.5 years, varying from 28 to 88 years. In our study, 63.3% of patients with mucormycosis were males and 37.8% were females, of which 55.7% (34) and 58.3% (21) were known diabetics, respectively. Previous history of diabetes mellitus was identified as an underlying comorbid condition in 56.7% of patients, while the rest were diagnosed with new-onset diabetes mellitus. Sugar levels ranged (on admission) from 112 to 494 mg/dL (median 212 mg/dL) for known diabetics and from 132 to 356 mg/dL (median 204 mg/dL) for newly diagnosed diabetics. Other comorbidities included hypertension (19.5%), ischemic heart disease (8.2%), chronic renal illness (3.09%), and one case (1.03%) of postoperative renal cell carcinoma (disease-free). The majority of cases (91.8%) were not vaccinated for COVID-19, while only two patients reported a history of vaccination with two doses, and six others had received only a single dose. At the 1-year follow-up, 57.7% of cases were disease-free, 30.9% had expired, and 11.3% were lost to follow-up. The mean glycated hemoglobin (HbA1c) at the time of admission was found to be statistically significant when compared between known diabetics and newly diagnosed ones [confidence interval (CI)-95%, p ≤ 0.01]. A total of seven patients from the newly diagnosed diabetic group no longer required medicines for diabetes at the end of 1 year (CI-95%, p ≤ 0.01). CONCLUSIONS AND RELEVANCE: Diabetes mellitus, particularly with poor glycemic control, was the single most important factor associated with and predictor of outcome. Contrary to the popular hypothesis, industrial oxygen and oxygen masks were not the reasons for the mucormycosis pandemic. Additionally, immunization against COVID provided protection not only from severe COVID but also from COVID-associated mucormycosis. It is recommended that patients with mucormycosis be followed for longer periods as a few patients could be suffering from transient diabetes, particularly against the backdrop of a pandemic.

Current paradigms in epigenetic anticancer therapeutics and future challenges.

Any alteration at the genetic or epigenetic level, may result in multiplex of diseases including tumorigenesis which ultimately results in the cancer development. Restoration of the normal epigenome by reversing the epigenetic alterations have been reported in tumors paving the way for development of an effective epigenetic treatment in cancer. However, delineating various epigenetic events has been a challenging task so far despite substantial progress in understanding DNA methylation and histone modifications during transcription of genes. Many inhibitors in the form of epigenetic drugs mostly targeting chromatin and histone modifying enzymes including DNA methyltransferase (DNMT) enzyme inhibitors and a histone deacetylases (HDACs) inhibitor, have been in use subsequent to the approval by FDA for cancer treatment. Similarly, other inhibitory drugs, such as FK228, suberoylanilide hydroxamic acid (SAHA) and MS-275, have been successfully tested in clinical studies. Despite all these advancements, still we see a hazy view as far as a promising epigenetic anticancer therapy is concerned. The challenges are to have more specific and effective inhibitors with negligible side effects. Moreover, the alterations seen in tumors are not well understood for which one has to gain deeper insight into the tumor pathology as well. Current review focusses on such epigenetic alterations occurring in cancer and the effective strategies to utilize such alterations for potential therapeutic use and treatment in cancer.

Experimental studies on the core-structure dependence of backward Brillouin gain in solid-core photonic crystal fibers.

Stimulated Brillouin scattering (SBS) in solid-core photonic crystal fibers (PCFs) differs significantly from that in standard optical fibers due to the tight confinement of both optical and acoustic fields in their µm-sized fiber cores, as resultantly evident in their Brillouin gain spectra. Despite many theoretical studies based on either simplified models or numerical simulations, the structural dependency of Brillouin gain spectra in small-core PCFs has not been characterized comprehensively using PCFs with elaborated parameter controls. In this work we report a comprehensive characterization on the core-structure dependences of backward SBS effects in solid-core PCFs that are drawn with systematically varied core-diameter, revealing several key trends of the fiber Brillouin spectrum in terms of its gain magnitude, Brillouin shift and multi-peak structure, which have not been reported in detail previously. Our work provides some practical guidance on PCF design for potential applications like Brillouin fiber lasers and Brillouin fiber sensing.

Studies on the morphology, phylogeny, and bioremediation potential of Penicillium citrinum and Paecilomyces variotii (Eurotiales) from oil-contaminated areas.

Crude oil pollution is one of the most arduous issues to address, as it is hazardous to both public health and the environment. The discovery of novel biosurfactants-producing fungi and bacteria is in high demand due to their excellent properties and wide range of applications. The aim of this research is to isolate a powerful biosurfactant-producing fungus from the crude oil site near Barauni oil refinery in Bihar, India. Standard protocols were used to collect samples from the site. An integrative taxonomic approach was used, which included morphological, molecular, and phylogenetic analysis. The use of plating samples on Bushnell-Hass (BH) media aided in the isolation of a fungal strain from an enrichment culture. Two fungal strains isolated from contaminated soils, Penicillium citrinum and Paecilomyces variotti, showed potent oil degrading activity in a single culture. For preliminary biosurfactants screening, drop collapse assays, oil spreading, and emulsification activity tests were used. The results showed that the cultures performed well in the screening test and were further evaluated for degradation capacity. Different treatment periods (0, 3, 6, 9, 12, and 15 days) were used to observe degradation in single cultures. A steady drop in pH, an alteration in optical density and an increase in carbon dioxide release showed the ability of fungal strain to degrade the crude oil in a single culture. Fungi mycelia provide a larger surface area for absorption and degradation of the pollutants in contaminated environment. They produce extracellular enzymes to degrade the oil, and at the same time absorb and utilise carbon, allowing them to remove toxic substances from the oil. Thus, they could be candidates for bioremediation of a hydrocarbon-contaminated site.

Potential therapeutic application of biophenols - plants secondary metabolites in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease showed that persistent inflammation in the joints, induces the cartilage destruction, bone erosion, and leukocyte infiltration in the synovium. RA mostly affects the joints of hands, feet, wrists, ankles, and knees. Each year, approximately 20-40 new cases are reported per lac population and the disease affects women more than men. The etiology of RA is still unknown, but many pathways have been identified as potential targets in its pathophysiology, including the PI3K/AKT signaling pathway, NF-κB signaling, Adenosine signaling, Wnt, SYK/BTK, and mTOR signaling pathways. Biophenol, plant secondary metabolite, is considered one of the most abundantly phytoconstituents to have potential anti-inflammatory effects associated with multiple pathways. These indicate that biophenols can be used for its protective effect on the development and symptoms of RA. The current review explores and discusses the role of different biophenols in the treatment of RA disease.

Postbiotics: an exposition on next generation functional food compounds- opportunities and challenges.

Consumer's interest for health promoting foods has reshaped the food industry to come up with novel biological compounds with diverse health benefits. Postbiotic are the cell fractions, or cell lysates which have emerged as potential functional food compounds during the last decade. The health benefits of postbiotic are well established while attempts are underway to understand their interaction, production, processing and safety. The review explore the challenges and opportunities to devise better growth mediums, cell lysis and extraction, characterization, stability and applications of postbiotics in both food and pharma industry along with the market trends, success stories and safety concerns regarding postbiotics. The scientific and commercial interest in postbiotic have resulted in extensive investigations and clinical documentation of various physiological benefits and additional bioactivity. The findings validate food and pharma application of the postbiotics and further emphasize on documentation of bioactivity and safety of these compounds.

Characterization of complete mitochondrial genome of three Horse flies of the genus Tabanus (Diptera: Tabanidae): comparative analysis.

BACKGROUND: Tabanidae (Horse-Flies or Deer-Flies) are one of the most economically important as well as medically significant haematophagous insect family within the order Diptera. Members of this group are also responsible for the mortality of substantial number of live-stock every year. Due to their pathogen transmission potential and vector competencies makes them an important insect group to study. Till now, mitochondrial genome of 18 species of tabanids were available. METHODS AND RESULTS: The complete mitogenome of three species T. diversifrons (15,809 bp), T. rubidus (15,878 bp) and T. tenens (15,872 bp) were generated by Next generation sequencing method. They consist 37 genes, with a positive AT skew and a negative GC skew. The gene order of these three species is similar to the typical gene arrangement of infra-order Tabanomorpha. Most of the tRNAs showed typical clover-leaf secondary structure except trnS1, which lacks the DHU arm. The sliding window analysis showed that the nad4L is the most conserved while atp8, and nad6 are the most variable genes. Moreover, the ratios of non-synonymous to synonymous substitution rates indicated that all PCGs under the purifying selection. Phylogeny revealed Chrysops and Haematopota are monophyletic while species of Hybomitra are nested within the polyphyletic clade of Tabanus. T. diversifrons exhibits sister relationship with Atylotus miser. Two morphologically divergent species T. rubidus and T. tenens are found to be genetically similar and indistinguishable by mitochondrial genome. CONCLUSIONS: The hypervariable genes like atp8 and nad6 can be used as molecular markers for the identification of recently diverged lineages of family Tabanidae. Further, to address uncertainties arising from the two morphological divergent species, it is imperative to obtain data from nuclear gene markers.

Co-drug development of gallic acid and metformin targeting the pro-inflammatory cytokines for the treatment of breast cancer.

It is well-documented that pro-inflammatory cytokines and inflammation play a significant role in the expansion of cancer disease. Gallic acid (GA), a natural compound, and metformin (Met), a synthetic drug exhibit potent anticancer potential via the distinct molecular mechanism. However, whether both these compounds can act synergistically to preclude and treat cancer is still unknown. This prompted us to scrutinize, the synergism between GA and Met, and that of a new co-drug synthesizing of GA and Met (GA-Met) and investigated the chemo-protective effect against breast cancer with possible intervention of cytokines. In vivo studies were based on chemical carcinogenesis, challenging breast tissue by dimethylbenz[α]anthracene (DMBA). Tumour incidence, tumour burden, pro-inflammatory cytokines in serum, breast, hepatic tissue, macroscopically and histological analysis of mammary tumours were carried out and estimated. GA, Met and GA-Met co-drug exhibited the inhibition of cell proliferation; higher reduction of cell proliferation was observed by GA-Met. The inhibitory effect of GA-Met was linked to cell cycle arrest at G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. GA-Met significantly inhibited the cytokines production along with protection against DMBA-induced hyperplasia. Taken altogether, the current result suggests that GA-Met co-drug endows a safe and protective effect against cancer metastasis and can possibly use for the treatment of human breast cancer.

Microbial diversity characterizations, associated pathogenesis and antimicrobial resistance profiling of Najafgarh drain.

The Najafgarh drain plays a significant role in the pollution of the Yamuna River, accounting for 40% of the total pollution. Therefore, it is crucial to investigate and analyze the microbial diversity, metabolic functional capacity, and antibiotic resistance genes (ARGs) present in the Najafgarh drain. Additionally, studying the water quality and its relationship with the proliferation of microorganisms in the drain is of utmost importance. Results obtained confirmed the deteriorated water quality as physico-chemical parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), dissolved oxygen (DO), and total suspended solids (TSS) in the range of 125-140, 400-460, 0-0.2, 25-140.4 mg/l respectively violated the standard permissible national and global standards. In addition, the next generation sequencing (NGS) analysis confirm the presence of genus such as Thauera, Arcobacter, Pseudomonas, Geobacter, Dechloromonas, Tolumonas, Sulfurospirullum, Desulfovibrio, Aeromonas, Bacteroides, Prevotella, Cloacibacterium, Bifidobacterium, Clostridium etc. along with 864 ARGs in the wastewater obtained from the Najafgarh drain. Findings confirm that the pathogenic species reported from this dataset possess severe detrimental impact on faunal and human health. Further, Pearson's r correlation analysis indicated that environmental variables, mainly total dissolved solids (TDS) and chemical oxygen demand (COD), play a pivotal role in driving microbial community structure of this heavily polluted drain. Thus, the poor water quality, presence of a microbial nexus, pathogenic markers, and ARGs throughout this drain confirmed that it would be one potential contributor to the dissemination of disease-causing agents (pathogens) to the household and drinking water supplies in the near future.

Comparative analysis of the two suborders of Thysanoptera and characterization of the complete mitochondrial genome of Thrips parvispinus.

Thrips parvispinus is a serious sucking pest on a number of economically important crops in the oriental region. It has gained importance recently for its drastic range extension distribution as an invasive pest. Here, the complete mitochondrial genome (15,067 bp) of Thrips parvispinus was sequenced and characterized. It possesses 37 genes and the putative noncoding region is duplicated. Comparative analyses of nucleotide diversity, skewness, codon usage bias, and selection pressure in mitochondrial protein-coding genes of the available 31 thrips mitogenomes (24 Terebrantia + 7 Tubulifera) were performed. Phylogenetic analysis showed a sister relationship of T. parvispinus to the clade (T. florum + T. hawaiiensis). Phylogenetic analyses formed the monophyly of subfamilies Phlaeothripinae and Idolothripinae within the family Phlaeothripidae (Suborder Tubulifera). Low nucleotide diversity was indicative of reversal of strand asymmetry in the Tubulifera. Neutrality analysis showed that directional mutation plays a major role in shaping codon usage bias in both suborders. Principal component analysis indicated distinct codon usage patterns in each suborder. Our data suggested weaker selection constrains on Terebrantia than in the Tubulifera. More tubuliferan mitogenomes are required to resolve previous classification hypotheses and elucidate genome evolution in these two suborders.