The potential of genome editing to create novel alleles of resistance genes in rice.

Rice, a staple food for a significant portion of the global population, faces persistent threats from various pathogens and pests, necessitating the development of resilient crop varieties. Deployment of resistance genes in rice is the best practice to manage diseases and reduce environmental damage by reducing the application of agro-chemicals. Genome editing technologies, such as CRISPR-Cas, have revolutionized the field of molecular biology, offering precise and efficient tools for targeted modifications within the rice genome. This study delves into the application of these tools to engineer novel alleles of resistance genes in rice, aiming to enhance the plant's innate ability to combat evolving threats. By harnessing the power of genome editing, researchers can introduce tailored genetic modifications that bolster the plant's defense mechanisms without compromising its essential characteristics. In this study, we synthesize recent advancements in genome editing methodologies applicable to rice and discuss the ethical considerations and regulatory frameworks surrounding the creation of genetically modified crops. Additionally, it explores potential challenges and future prospects for deploying edited rice varieties in agricultural landscapes. In summary, this study highlights the promise of genome editing in reshaping the genetic landscape of rice to confront emerging challenges, contributing to global food security and sustainable agriculture practices.

Exploring anticancer properties of the phytoconstituents and comparative analysis of their chemical space parameters with USFDA-approved synthetic anticancer agents.

The present review article thoroughly analyses natural products and their derived phytoconstituents as a rich source of plausible anticancer drugs. The study thoroughly explores the chemical components derived from various natural sources, thus emphasizing their unique structural characteristics and therapeutic potential as an anticancer agent. The review contains the critical chemical constituents' in-depth molecular mechanisms, their source's chemical structures and the categories. The review also comprises an exhaustive and comprehensive analysis of different chemical spacing parameters of the anticancer agents derived from natural products. It compares them with USFDA-approved synthetic anticancer drugs up to 2020, thus providing a meaningful understanding of the relationship between natural and synthetic compounds portraying the anticancer assets. The review also delves more deeply into the chemical analysis of the heterocyclic moieties from the natural product arena, illustrating the anticancer mechanisms. The present article is, therefore, expected to serve as a valuable resource for natural product and medicinal chemists, encouraging and promoting an integrated approach to exploit the potential of natural products in drug discovery development and translational research, which have a prerequisite of bench to bedside approach. The work could guide researchers toward innovative approaches for the ever-evolving field of anticancer drug discovery.

Knockdown of SCN5A alters metabolic-associated genes and aggravates hypertrophy in the cardiomyoblast.

SCN5A mutations have been reported to cause various cardiomyopathies in humans. Most of the SCN5A mutations causes loss of function and thereby, alters the overall cellular function. Therefore, to understand the loss of SCN5A function in cardiomyocytes, we have knocked down the SCN5A gene (SCN5A-KD) in H9c2 cells and explored the cell phenotype and molecular behaviors in the presence and absence of isoproterenol (ISO), an adrenergic receptor agonist that induces cardiac hypertrophy. Expression of several genes related to hypertrophy, inflammation, fibrosis, and energy metabolism pathways were evaluated. It was found that the mRNA expression of hypertrophy-related gene, brain (B-type) natriuretic peptide (BNP) was significantly increased in SCN5A-KD cells as compared to 'control' H9c2 cells. There was a further increase in the mRNA expressions of BNP and ßMHC in SCN5A-KD cells after ISO treatment compared to their respective controls. Pro-inflammatory cytokine, tumor necrosis factor-alpha expression was significantly increased in 'SCN5A-KD' H9c2 cells. Further, metabolism-related genes like glucose transporter type 4, cluster of differentiation 36, peroxisome proliferator-activated receptor alpha, and peroxisome proliferator-activated receptor-gamma were significantly elevated in the SCN5A-KD cells as compared to the control cells. Upregulation of these metabolic genes is associated with increased ATP production. The study revealed that SCN5A knock-down causes alteration of gene expression related to cardiac hypertrophy, inflammation, and energy metabolism pathways, which may promote cardiac remodelling and cardiomyopathy.

Synthesis of ciprofloxacin-linked 1,2,3-triazole conjugates as potent antibacterial agents using click chemistry: exploring their function as DNA gyrase inhibitors via in silico- and in vitro-based studies.

The antibacterial efficacy of some newly developed C-3 carboxylic group-containing ciprofloxacin-linked 1,2,3-triazole conjugates was studied. Twenty-one compounds from three different series of triazoles were synthesized using click chemistry and evaluated for their antibacterial activity against nine different pathogenic strains, including three Gram-positive strains, i.e. Enterococcus faecalis (ATCC29212), Staphylococcus aureus (ATCC25923), Staphylococcus epidermidis (clinical isolate), and six Gram-negative bacterial strains, i.e. Escherichia coli (ATCC25922), Pseudomonas aeruginosa (ATCC27853), Salmonella typhi (clinical isolate), Proteus mirabilis (clinical isolate), Acinetobacter baumannii (clinical isolate) and Klebsiella pneumonia (clinical isolate). Among the compounds, 10, 10a, 10b, 10c, 10d, 11a, 11f, 12c, 12e and 12f showed excellent activity with MIC values upto 12.5 µg mL-1, whereas the control ciprofloxacin showed MIC values of 0.781-25 µg mL-1 towards various strains. In addition, the low toxicity profile of the synthesized molecules revealed that they are potent antibiotics. Molecular docking and MD analysis were performed using the protein structure of E. coli DNA gyrase B, which was further corroborated with an in vitro assay to evaluate the inhibition of DNA gyrase. The analysis revealed that compound 10b was the most potent inhibitor of DNA gyrase compared to ciprofloxacin, which was employed as the positive control. Furthermore, the structure of two title compounds (11a and 12d) was characterized using single-crystal analysis.

Rapid HPLC method reveals dynamic shifts in coenzyme Q redox state.

Ubiquinol or coenzyme Q (CoQ) is a lipid-soluble electron carrier in the respiratory chain and an electron acceptor for various enzymes in metabolic pathways that intersect at this cofactor hub in the mitochondrial inner membrane. The reduced form of CoQ is an antioxidant, which protects against lipid peroxidation. In this study, we have optimized a UV-detected HPLC method for CoQ analysis from biological materials, which involves a rapid single-step extraction into n-propanol followed by direct sample injection onto a column. Using this method, we have measured the oxidized, reduced, and total CoQ pools and monitored shifts in the CoQ redox status in response to cell culture conditions and bioenergetic perturbations. We find that hypoxia or sulfide exposure induces a reductive shift in the intracellular CoQ pool. The effect of hypoxia is, however, rapidly reversed by exposure to ambient air. Interventions at different loci in the electron transport chain can induce sizeable redox shifts in the oxidative or reductive direction, depending on whether they are up- or downstream of complex III. We have also used this method to confirm that CoQ levels are higher and more reduced in murine heart versus brain. In summary, the availability of a convenient HPLC-based method described herein will facilitate studies on CoQ redox dynamics in response to environmental, nutritional, and endogenous alterations.

One-dimensional proximity superconductivity in the quantum Hall regime.

Extensive efforts have been undertaken to combine superconductivity and the quantum Hall effect so that Cooper-pair transport between superconducting electrodes in Josephson junctions is mediated by one-dimensional edge states1-6. This interest has been motivated by prospects of finding new physics, including topologically protected quasiparticles7-9, but also extends into metrology and device applications10-13. So far it has proven challenging to achieve detectable supercurrents through quantum Hall conductors2,3,6. Here we show that domain walls in minimally twisted bilayer graphene14-18 support exceptionally robust proximity superconductivity in the quantum Hall regime, allowing Josephson junctions to operate in fields close to the upper critical field of superconducting electrodes. The critical current is found to be non-oscillatory and practically unchanging over the entire range of quantizing fields, with its value being limited by the quantum conductance of ballistic, strictly one-dimensional, electronic channels residing within the domain walls. The system described is unique in its ability to support Andreev bound states at quantizing fields and offers many interesting directions for further exploration.

Unusual Case Report of Headache in 10-Year-Old Female Child.

According to the literature, transverse sinus hypoplasia is not a normal variant and has a serious potential effect on cerebral blood flow. We are presenting a rare case of chronic headache due to severe hypoplasia of the left transverse and sigmoidal sinus. A 12-year-old female girl was admitted with a complaint of gradual progressive severe headache, throbbing in nature, confined to a bitemporal and frontal region in the last 4-5 months. Headache is not associated with fever, vomiting, photophobia, or vision problems. The child had no history of recurrent running nose, refractory vision, ear discharge, head trauma, exanthemata rash, or any drug history. On examination, the child was conscious and oriented. Vital signs are normal. The child was neurologically normal and had no focal signs. Other systemic examinations were normal. Based on History and examination, differential diagnosis was made, like Pseudo tumor cerebri, migraine, deep vein sinus thrombosis, and functional and Posterior fossa tumor. The child had normal routine investigations like complete blood count, electrolyte, and D-dimer. The fundoscopy was normal. In MRI, brain hypoplasia of the left transverse and sinusoidal sinus was suspected and confirmed by MRI venography. Thus, for any patient in an emergency with a chronic headache without focal signs and normal fundoscopy, one deferential should be considered for transverse and sigmoid sinus hypoplasia.

H2S preconditioning induces long-lived perturbations in O2 metabolism.

Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half-maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury and/or prolonging the shelf life of biologics like platelets.

Sulfide oxidation promotes hypoxic angiogenesis and neovascularization.

Angiogenic programming in the vascular endothelium is a tightly regulated process for maintaining tissue homeostasis and is activated in tissue injury and the tumor microenvironment. The metabolic basis of how gas signaling molecules regulate angiogenesis is elusive. Here, we report that hypoxic upregulation of ·NO in endothelial cells reprograms the transsulfuration pathway to increase biogenesis of hydrogen sulfide (H2S), a proangiogenic metabolite. However, decreased H2S oxidation due to sulfide quinone oxidoreductase (SQOR) deficiency synergizes with hypoxia, inducing a reductive shift and limiting endothelial proliferation that is attenuated by dissipation of the mitochondrial NADH pool. Tumor xenografts in whole-body (WBCreSqorfl/fl) and endothelial-specific (VE-cadherinCre-ERT2Sqorfl/fl) Sqor-knockout mice exhibit lower mass and angiogenesis than control mice. WBCreSqorfl/fl mice also exhibit decreased muscle angiogenesis following femoral artery ligation compared to control mice. Collectively, our data reveal the molecular intersections between H2S, O2 and ·NO metabolism and identify SQOR inhibition as a metabolic vulnerability for endothelial cell proliferation and neovascularization.

Identification of a microbial sub-community from the feral chicken gut that reduces Salmonella colonization and improves gut health in a gnotobiotic chicken model.

A complex microbial community in the gut may prevent the colonization of enteric pathogens such as Salmonella. Some individual or a combination of species in the gut may confer colonization resistance against Salmonella. To gain a better understanding of the colonization resistance against Salmonella enterica, we isolated a library of 1,300 bacterial strains from feral chicken gut microbiota which represented a total of 51 species. Using a co-culture assay, we screened the representative species from this library and identified 30 species that inhibited Salmonella enterica subspecies enterica serovar Typhimurium in vitro. To improve the Salmonella inhibition capacity, from a pool of fast-growing species, we formulated 66 bacterial blends, each of which composed of 10 species. Bacterial blends were more efficient in inhibiting Salmonella as compared to individual species. The blend that showed maximum inhibition (Mix10) also inhibited other serotypes of Salmonella frequently found in poultry. The in vivo effect of Mix10 was examined in a gnotobiotic and conventional chicken model. The Mix10 consortium significantly reduced Salmonella load at day 2 post-infection in gnotobiotic chicken model and decreased intestinal tissue damage and inflammation in both models. Cell-free supernatant of Mix10 did not show Salmonella inhibition, indicating that Mix10 inhibits Salmonella through either nutritional competition, competitive exclusion, or through reinforcement of host immunity. Out of 10 species, 3 species in Mix10 did not colonize, while 3 species constituted more than 70% of the community. Two of these species were previously uncultured bacteria. Our approach could be used as a high-throughput screening system to identify additional bacterial sub-communities that confer colonization resistance against enteric pathogens and its effect on the host.IMPORTANCESalmonella colonization in chicken and human infections originating from Salmonella-contaminated poultry is a significant problem. Poultry has been identified as the most common food linked to enteric pathogen outbreaks in the United States. Since multi-drug-resistant Salmonella often colonize chicken and cause human infections, methods to control Salmonella colonization in poultry are needed. The method we describe here could form the basis of developing gut microbiota-derived bacterial blends as a microbial ecosystem therapeutic against Salmonella.

From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease.

The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like ß-glucuronidases and ß-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders.

Kagome Quantum Oscillations in Graphene Superlattices.

Electronic spectra of solids subjected to a magnetic field are often discussed in terms of Landau levels and Hofstadter-butterfly-style Brown-Zak minibands manifested by magneto-oscillations in two-dimensional electron systems. Here, we present the semiclassical precursors of these quantum magneto-oscillations which appear in graphene superlattices at low magnetic field near the Lifshitz transitions and persist at elevated temperatures. These oscillations originate from Aharonov-Bohm interference of electron waves following open trajectories that belong to a kagome-shaped network of paths characteristic for Lifshitz transitions in the moire superlattice minibands of twistronic graphenes.

Recording Postprandial Glucose Reactions with Potato Starch Structural Improvements.

The current study is aimed at modifying the structural makeup of potato starch through the application of heat and moisture to better control the postprandial glycemic response. Heat-moisture treatment (HMT) was used to prepare potato starch using different moisture levels and temperatures. The samples were digested with pancreatin to determine the % of easily digestible, slowly digestible, and resistant starch. Subjects were given pudding made with HMT potato starch, and their postprandial glycemic response was tracked by measuring their blood glucose levels. In addition, incremental and total incremental areas under the curve (IAUC, TIAUC) were also assessed. The current findings of in vitro enzymatic digestibility of potato starch showed inconsistent results as measured at different time intervals. Adding moisture and heating the mixture to 30 and 70°C both increased the amount of rapidly digestible starch in all of the treatments from 20 to 40%. The maximum value of slowly digestible starch was 43.63% when the sample was heated to 30°C with a moisture content of 30%. The highest value (68.46%) for resistant starch was achieved at 20% moisture level and 30°C. After eating pudding, blood sugar spiked for the first 60 and 90 min before gradually dropping off over the next 240 min. As a whole, the highest IAUC and TIAUC values, as well as the glycemic index and load, were observed in potato starch heated to 70°C, which contained 40% moisture. Most parameters achieved their highest values when 40% moisture was added and the heat was applied at 70°C.

H 2 S preconditioning induces long-lived perturbations in O 2 metabolism.

Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H 2 S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H 2 S preconditioning increases P 50(O2) , the O 2 pressure for half maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24-48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H 2 S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury, and/or prolonging shelf life of biologics like platelets.

Assessment and identification of bioactive metabolites from terrestrial Lyngbya spp. responsible for antioxidant, antifungal, and anticancer activities.

Lyngbya from fresh and marine water produces an array of pharmaceutically bioactive therapeutic compounds. However, Lyngbya from agricultural soil is still poorly investigated. Hence, in this study, the bioactive potential of different Lyngbya spp. extract was explored. Intracellular petroleum ether extract of L. hieronymusii K81 showed the highest phenolic content (626.22 ± 0.65 µg GAEs g-1 FW), while intracellular ethyl acetate extract of L. aestuarii K97 (74.02 ± 0.002 mg QEs g-1 FW) showed highest flavonoid content. Highest free radical scavenging activity in terms of ABTS•+ was recorded in intracellular methanolic extract of Lyngbya sp. K5 (97.85 ± 0.068%), followed by L. wollei K80 (97.22 ± 0.059%) while highest DPPH• radical scavenging activity observed by intracellular acetone extract of Lyngbya sp. K5 (54.59 ± 0.165%). All the extracts also showed variable degrees of antifungal activities against Fusarium udum, F. oxysporum ciceris, Colletotrichum capsici, and Rhizoctonia solani. Further, extract of L. wollei K80 and L. aestuarii K97 showed potential anticancer activities against MCF7 (breast cancer) cell lines. GC-MS analyses of intracellular methanolic extract of L. wollei K80 showed the dominance of PUFAs with 9,12,15-octadecatrienoic acid, methyl ester, (Z,Z,Z) as the most abundant bioactive compound. On the other hand, the extracellular ethyl acetate extract of L. aestuarii K97 was rich in alkanes and alkenes with 1-hexyl-2-nitrocyclohexane as the most predominant compound. Extracts of Lyngbya spp. rich in novel secondary metabolites such as PUFAs, alkanes, and alkenes can be further explored as an alternative and low-cost antioxidant and potential apoptogens for cancer therapy.

Targeted editing of multiple homologues of GTR1 and GTR2 genes provides the ideal low-seed, high-leaf glucosinolate oilseed mustard with uncompromised defence and yield.

Glucosinolate content in the two major oilseed Brassica crops-rapeseed and mustard has been reduced to the globally accepted Canola quality level (<30 µmoles/g of seed dry weight, DW), making the protein-rich seed meal useful as animal feed. However, the overall lower glucosinolate content in seeds as well as in the other parts of such plants renders them vulnerable to biotic challenges. We report CRISPR/Cas9-based editing of glucosinolate transporter (GTR) family genes in mustard (Brassica juncea) to develop ideal lines with the desired low seed glucosinolate content (SGC) while maintaining high glucosinolate levels in the other plant parts for uncompromised plant defence. Use of three gRNAs provided highly efficient and precise editing of four BjuGTR1 and six BjuGTR2 homologues leading to a reduction of SGC from 146.09 µmoles/g DW to as low as 6.21 µmoles/g DW. Detailed analysis of the GTR-edited lines showed higher accumulation and distributional changes of glucosinolates in the foliar parts. However, the changes did not affect the plant defence and yield parameters. When tested against the pathogen Sclerotinia sclerotiorum and generalist pest Spodoptera litura, the GTR-edited lines displayed a defence response at par or better than that of the wild-type line. The GTR-edited lines were equivalent to the wild-type line for various seed yield and seed quality traits. Our results demonstrate that simultaneous editing of multiple GTR1 and GTR2 homologues in mustard can provide the desired low-seed, high-leaf glucosinolate lines with an uncompromised defence and yield.

National Cancer Registry of Pakistan: First Comprehensive Report of Cancer Statistics 2015-2019.

OBJECTIVE: To compile a comprehensive national cancer registry report of Pakistan by merging and analysing cancer registration data received from major functional cancer registries in various parts of Pakistan. STUDY DESIGN: Observational study. Place and Duration of the Study: Health Research Institute (HRI), National Institutes of Health (NIH), Islamabad, from 2015-2019. METHODOLOGY: Data from major cancer registries which included 'Punjab Cancer Registry (PCR), 'Karachi Cancer Registry (KCR)', 'Pakistan Atomic Energy Commission (PAEC) Cancer Registry', Armed Forces Institute of Pathology (AFIP) Cancer Registry, Nishtar Medical University Hospital Multan (NMH), and Shifa International Hospital, Islamabad (SIH) registries were pooled, cleared, and analysed at HRI. RESULTS: A total of 269,707 cancer cases were analysed. Gender-wise 46.7% were males and 53.61% were females. As per province-wise distribution, 45.13% of cases were from Punjab, 26.83% from Sindh, 16.46% from Khyber Pakhtunkhwa (KP), and 3.52% from Baluchistan. Both genders combined, 'breast cancer' 57633 (21.4%) was the most common cancer. In males, the top-5 cancers in order of frequency/percenatages were 'oral' 14477 (11.6%), 'liver' 8398 (6.73%), colorectal 8024 (6.43%), 'lung' 7547 (6.05%) and 'prostate' 7322 (5.87% cancers). In females, causes of the top-5-cancers included 'breast' 56250 (38.8%), 'ovary' 8823 (6.09%), 'oral' 7195 (4.97%), 'cervix' 6043 (4.17%), and 'colorectal' 4860 (3.36%) cancers. In children 'Leukemia' 1626 (14.50%) and in adolescents 'Bone' 880 (14%) were the leading malignancies. CONCLUSION: Breast cancer is the most common cancer in females touching epidemic proportions while 'oral cancer' which is the leading cancer in males ranks third in frequency in females. Like 'oral cancer' which shows a strong correlation with chewing, other common cancers in Pakistan including liver cancer, lung cancer, and cervical cancer are also largely preventable as showed a strong correlation with hepatitis B and C, smoking, and high-risk human papillomavirus. KEY WORDS: National Cancer Registry, Health Research Institute - NIH, Islamabad, Pakistan.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile.

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Monkeypox virus: phylogenomics, host-pathogen interactome and mutational cascade.

While the world is still recovering from the Covid-19 pandemic, monkeypox virus (MPXV) awaits to cause another global outbreak as a challenge to all of mankind. However, the Covid-19 pandemic has taught us a lesson to speed up the pace of viral genomic research for the implementation of preventive and treatment strategies. One of the important aspects of MPXV that needs immediate insight is its evolutionary lineage based on genomic studies. Utilizing high-quality isolates from the GISAID (Global Initiative on Sharing All Influenza Data) database, primarily sourced from Europe and North America, we employed a SNP-based whole-genome phylogeny method and identified four major clusters among 628 MPXV isolates. Our findings indicate a distinct evolutionary lineage for the first MPXV isolate, and a complex epidemiology and evolution of MPXV strains across various countries. Further analysis of the host-pathogen interaction network revealed key viral proteins, such as E3, SPI-2, K7 and CrmB, that play a significant role in regulating the network and inhibiting the host's cellular innate immune system. Our structural analysis of proteins E3 and CrmB revealed potential disruption of stability due to certain mutations. While this study identified a large number of mutations within the new outbreak clade, it also reflected that we need to move fast with the genomic analysis of newly detected strains from around the world to develop better prevention and treatment methods.