BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis.

For tumors to progress efficiently, cancer cells must overcome barriers of oxidative stress. Although dietary antioxidant supplementation or activation of endogenous antioxidants by NRF2 reduces oxidative stress and promotes early lung tumor progression, little is known about its effect on lung cancer metastasis. Here, we show that long-term supplementation with the antioxidants N-acetylcysteine and vitamin E promotes KRAS-driven lung cancer metastasis. The antioxidants stimulate metastasis by reducing levels of free heme and stabilizing the transcription factor BACH1. BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. Targeting BACH1 normalized glycolysis and prevented antioxidant-induced metastasis, while increasing endogenous BACH1 expression stimulated glycolysis and promoted metastasis, also in the absence of antioxidants. We conclude that BACH1 stimulates glycolysis-dependent lung cancer metastasis and that BACH1 is activated under conditions of reduced oxidative stress.

Presentation, management, and early outcomes of young acute coronary syndrome patients- analysis of 23,560 South Asian patients from 2012 to 2021.

BACKGROUND: There is dearth of literature addressing early outcomes of acute coronary syndrome (ACS) among young patients, particularly South Asians descent who are predisposed to premature coronary artery disease (CAD). Therefore, we compared presentation, management, and early outcomes of young vs. old ACS patients and explored predictors of in-hospital mortality. METHODS: We extracted data of 23,560 ACS patients who presented at Tabba Heart Institute, Karachi, Pakistan, from July 2012-June 2020, from the Chest pain-MI-Registry™. We categorized data into young ≤ 45 and old ACS patients > 45 years. Chi-sq/Fischer exact tests were used to assess the difference between presentation, disease management, and in-hospital mortality between both groups. Logistic regression was used to determine odds ratio along with 95% confidence interval of factors associated with early mortality. RESULTS: The younger patients were 12.2% and women 23.5%. The prevalence of dyslipidemia (34.5% vs. 22.4%), diabetes (52.1% vs. 27.4%), and hypertension (68.3% vs. 42.9%) was higher in older patients. Family history of premature CAD (18.1% vs. 32.7%), smoking (40.0% vs. 22.9%), and smokeless tobacco use (6.5% vs. 8.4%) were lower in older patients compared to younger ones. Younger patients were more likely to present with STEMI (33.2% vs. 45%). The median symptom-to-door time was 125 min longer (p-value < 0.01) in the young patients compared to the older age group. In-hospital mortality (4.3% vs. 1.7%), cardiac arrest (1.9% vs. 0.7%), cardiogenic shock (1.9% vs. 0.9%), and heart failure (1% vs. 0.6%) were more common in older patients. After adjusting for other factors, younger age (AOR 0.6, 95% CI 1.5-3.7) had significantly lesser odds of in-hospital mortality. Other factors associated with early mortality included women, family history of premature CAD, STEMI, Killip class III and IV, coronary angiography, revascularization, CABG, and use of aspirin and beta blockers within the first 24 h. CONCLUSION: We found every tenth ACS patient was younger than 45 years of age despite a lesser number of comorbidities such as hypertension and diabetes. Overall, the in-hospital prognosis of young patients was more favorable than that of older patients. The study emphasizes the need for tailored primary prevention programs for ACS, considering the varying risks among different age groups.

Effects of virtual reality versus motor imagery versus routine physical therapy in patients with parkinson's disease: a randomized controlled trial.

BACKGROUND: Parkinson's Disease (PD) is the second most common progressive neurodegenerative disorder, mostly affecting balance and motor function caused mainly by a lack of dopamine in the brain. The use of virtual reality (VR) and motor imagery (MI) is emerging as an effective method of rehabilitation for people with Parkinson's disease. Motor imagery and virtual reality have not been compared in patients with Parkinson's disease. This randomized clinical trial is unique to compare the effects of virtual reality with routine physical therapy, motor imagery with routine physical therapy, and routine physical therapy alone on balance, motor function, and activities of daily living in patients with Parkinson's disease. METHODS: A total of sixty patients with Parkinson's disease were randomized into three groups using lottery method; twenty with virtual reality therapy in addition to physical therapy (group A = VR + RPT), twenty with imagery therapy in addition to physical therapy (group B = MI + RPT), and twenty were treated with only routine physical therapy (group C = RPT). All patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) for motor function and activities of daily living, the Berg balance scale (BBS) for balance, and the Activities-specific Balance Confidence Scale (ABCs) for balance confidence at baseline, six and twelve weeks, and one month after treatment discontinuation. The one-way ANOVA was used to compare the outcomes between three groups, and the repeated measures ANOVA was used to compare the outcomes within each of the three groups at a significance level of p-value = 0.05. RESULTS: According to UPDRS III, the VR + RPT group showed significant improvement in motor function, compared to the MI + RPT and RPT groups, as the Mean ± SD at baseline was 33.95 ± 3.501 and at the 12-week assessment was 17.20 ± 9.451 with a p-value = 0.001. In the VR + RPT group, the BBS score at baseline was 37.15 ± 3.437 and at 12th week was 50.10 ± 4.897 with a p-value = 0.019. Among the VR + RPT group, the ABCS score showed significant improvement as the M ± SD at baseline was 57.95 ± 4.629, and at the 12th week was 78.59 ± 6.386 with a p-value = 0.010. At baseline, the UPDRS II for activities of daily living in the VR + RPT group was 25.20 ± 3.036 and at 12th week it was 15.30 ± 2.364 with p-value of 0.000. CONCLUSION: The current study found that the combination of VR and RPT proved to be the most effective treatment method for improving balance, motor function, and activities of daily living in patients with Parkinson's disease when compared to MI + RPT or RPT alone.

Deciphering the biodesulfurization pathway employing marine mangrove Bacillus aryabhattai strain NM1-A2 according to whole genome sequencing and transcriptome analyses.

In the biogeochemical cycle, sulfur oxidation plays a vital role and is typically referred to as the elemental sulfur or reductive sulfide oxidation process. This study aimed to characterize a subtropical mangrove-isolated bacterial strain using biochemical, whole-genome, and transcriptome sequencing analyses to enhance our understanding of sulfur metabolism and biodegradation from a molecular genetic perspective. Strain NM1-A2 was characterized as Gram-positive and found to have a close molecular phylogenetic relationship with Bacillus aryabhattai. NM1-A2 efficiently converted dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) via a 4S pathway with 95% efficiency, using enzymes encoded by the dsz operon (dszA, dszB, and dszC), which determine monooxygenases (DszA & DszC) and desulfinase (DszB). The whole-genome sequence of NM1-A2 had a length of approximately 5,257,678 bp and included 16 sulfur metabolism-related genes, featuring the ABC transport system, small subunit (ssu) and cysteine (cys) gene families, and adenosine 5'-phosphosulfate (APS) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthesis-related genes. Transcriptomic analysis of NM1-A2 using three sulfur groups-magnesium sulfate (MS), sulfur powder (SP), and sodium thiosulfate (ST) resulted in a significant number of differentially expressed genes (1200, 2304, and 2001, respectively). This analysis revealed that intracellular cysteine concentration directly regulated the expression of cys and ssu genes. Sulfate did not directly affect cys gene expression but repressed ssu gene expression. The cys gene expression levels decreased during the conversion of sulfate to sulfide and cysteine. The transcriptomic data was validated by analyzing the expression patterns of NM1-A2 using real-time quantitative PCR validation analysis. The expression levels of cysl, mccB, and nrnA were significantly upregulated, while cysH, metB, and sat were downregulated in the SP, ST, and MS groups, respectively. This research contributes to our understanding of marine mangrove microorganisms' bacterial efficiency through characterization, whole-genome, and transcriptome sequencing-based molecular degradation of organic compounds in the mangrove ecosystem, which may enhance nutrient availability.

Effect of ammonium stress on phosphorus solubilization of a novel marine mangrove microorganism Bacillus aryabhattai NM1-A2 as revealed by integrated omics analysis.

BACKGROUND: Phosphorus is one of the essential nutrients for plant growth. Phosphate-solubilizing microorganisms (PSMs) can alleviate available P deficiency and enhance plant growth in an eco-friendly way. Although ammonium toxicity is widespread, there is little understanding about the effect of ammonium stress on phosphorus solubilization (PS) of PSMs. RESULTS: In this study, seven PSMs were isolated from mangrove sediments. The soluble phosphate concentration in culture supernatant of Bacillus aryabhattai NM1-A2 reached a maximum of 196.96 mg/L at 250 mM (NH4)2SO4. Whole-genome analysis showed that B. aryabhattai NM1-A2 contained various genes related to ammonium transporter (amt), ammonium assimilation (i.e., gdhA, gltB, and gltD), organic acid synthesis (i.e., ackA, fdhD, and idh), and phosphate transport (i.e., pstB and pstS). Transcriptome data showed that the expression levels of amt, gltB, gltD, ackA and idh were downregulated, while gdhA and fdhD were upregulated. The inhibition of ammonium transporter and glutamine synthetase/glutamate synthase (GS/GOGAT) pathway contributed to reducing energy loss. For ammonium assimilation under ammonium stress, accompanied by protons efflux, the glutamate dehydrogenase pathway was the main approach. More 2-oxoglutarate (2-OG) was induced to provide abundant carbon skeletons. The downregulation of formate dehydrogenase and high glycolytic rate resulted in the accumulation of formic acid and acetic acid, which played key roles in PS under ammonium stress. CONCLUSIONS: The accumulation of 2-OG and the inhibition of GS/GOGAT pathway played a key role in ammonium detoxification. The secretion of protons, formic acid and acetic acid was related to PS. Our work provides new insights into the PS mechanism, which will provide theoretical guidance for the application of PSMs.

Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy.

Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. Although NK cell-specific checkpoint targets such as NKG2A and KIRs are currently being evaluated in clinical trials, the clinical impact of NK cells on the PD1 cascade is less well understood compared to T cells. Furthermore, while NK cells have effector activity within the TME, under continuous ligand exposure, NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. Due to above-mentioned factors, we designed novel NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3ζ to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PD-L1+ target cells. Additionally, PD1-CSR+ NK cells infiltrated and killed tumor spheroids. While primary NK cells (pNK), expressing native PD1, showed decreased degranulation and cytokine production against PD-L1+ target cells by twofold, PD1-CSR+ pNK cells demonstrated increased activity upon PD-L1+ target cell recognition and enhanced antibody-dependent cellular cytotoxicity. PD1-CSR+ pNK cells from patients with MM increased degranulation and cytokine expression against autologous CD138+PD-L1+ malignant plasma cells. Taken together, the present results demonstrate that PD1-CSR+ NK cells enhance and sustain potent anti-tumor activity in a PD-L1+ microenvironment and thus represent a promising strategy to advance adoptive NK cell-based immunotherapies toward PD-L1+ cancers.

Molecular characterization and risk factors of oral high-risk human papillomavirus among females in Punjab, Pakistan.

BACKGROUND: The development of oral and oropharyngeal cancers is associated with human papillomavirus (HPV) infection. However, debate exists about the prevalence of high-risk oral HPV (HR-HPV) and its associated risk factors. This study evaluated the distribution of genotypes and associated risk factors of oral HR-HPV infection in the normal oral mucosa of the Pakistani female population with general gynecological problems. METHODS: A total of 200 females from a regional gynecological hospital in Pakistan were included in this cross-sectional study. A self-administered questionnaire was carried out, followed by the study participants' oral and dental examinations. Whole saliva was collected by a drooling method. The viral DNA extraction and oral HR-HPV genotyping were detected via real-time polymerase chain reaction. RESULTS: Among the 200 females (mean age, 37.76 years), 22 females (11%) were positive for oral HR-HPV DNA. Single oral HR-HPV infection was seen in 8%, whereas co-infection was observed in 3% with HPV16 and HPV18 most common genotypes. Comparison of the risk factors like oral sex history odds ratio (OR 8.21, 95% confidence interval [CI] 1.85-28.16; p < 0.005), and open-mouth kissing (OR, 5.17; 95% CI 1.48-27.41; p = 0.005) with oral HR-HPV infection was found to be significantly associated. CONCLUSION: In Pakistan, oral HR-HPV-positive infection is not uncommon; HPV16 and HPV18 are the most frequent genotypes. Furthermore, this study also provides data that oral HR-HPV positive infection was significantly associated with sexual behaviors. Therefore, preventive health efforts, like health education and vaccination, should be practiced.

Efficacy of anti-CD3 monoclonal antibodies in delaying the progression of recent-onset type 1 diabetes mellitus: A systematic review, meta-analyses and meta-regression.

AIM: Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes. METHODS: A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment. RESULTS: In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed. CONCLUSION: The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.

Integration of Microbial Transformation Mechanism of Polyphosphate Accumulation and Sulfur Cycle in Subtropical Marine Mangrove Ecosystems with Spartina alterniflora Invasion.

Excessive phosphorus can lead to eutrophication in marine and coastal ecosystems. Sulfur metabolism-associated microorganisms stimulate biological phosphorous removal. However, the integrating co-biotransformation mechanism of phosphorus and sulfur in subtropical marine mangrove ecosystems with Spartina alterniflora invasion is poorly understood. In this study, an ecological model of the coupling biotransformation of sulfur and phosphorus is constructed using metagenomic analysis and quantitative polymerase chain reaction strategies. Phylogenetic analysis profiling, a distinctive microbiome with high frequencies of Gammaproteobacteria and Deltaproteobacteria, appears to be an adaptive characteristic of microbial structures in subtropical mangrove ecosystems. Functional analysis reveals that the levels of sulfate reduction, sulfur oxidation, and poly-phosphate (Poly-P) aggregation decrease with increasing depth. However, at depths of 25-50 cm in the mangrove ecosystems with S. alterniflora invasion, the abundance of sulfate reduction genes, sulfur oxidation genes, and polyphosphate kinase (ppk) significantly increased. A strong positive correlation was found among ppk, sulfate reduction, sulfur oxidation, and sulfur metabolizing microorganisms, and the content of sulfide was significantly and positively correlated with the abundance of ppk. Further microbial identification suggested that Desulfobacterales, Anaerolineales, and Chromatiales potentially drove the coupling biotransformation of phosphorus and sulfur cycling. In particular, Desulfobacterales exhibited dominance in the microbial community structure. Our findings provided insights into the simultaneous co-biotransformation of phosphorus and sulfur bioconversions in subtropical marine mangrove ecosystems with S. alterniflora invasion.

Microsatellite-based diversity analysis and the development of core-set germplasm in Pakistani barley lines.

Illustrating the population structure and genetic diversity in selected germplasm resources (after three year multi locations trials) plays a key role which directly utilize the selection of lines in a population for accumulative trait breeding in crops. In order to further understand, the structure of population and genetic variability, we explored 100 selected lines, cultivated for three consecutive years (2016-2019) in swat, University of Malakand, Khyber Pakhtunkhwa Pakistan and Provinces of China (Chongqing and Beijing) with 33 mapped SSR markers. The integrated population structure analysis in a core of hundred germplasm with Pakistani origin with three approved commercial barley cultivars have strong stratification that allowed their division into four major subpopulations (i.e. PI, PII, PIII and PIV) and an admixture subpopulation, with 52, 9, 15 and 27 germplasm respectively. A total of 133 alleles were identified with mean value of 0.80 Polymorphic information content. The number of alleles detected by the system varied from two alleles amplified to as six with an average of 4.03 per SSR marker pair. The gene diversity ranged from 0.56 to 0.98 with an average of 0.82 in selected germplasm resources. Based on the SSR data, the 100 selected germplasm with three cultivars were classified into four main phylogenetic Linages (LI, LII, LIII and LIV) which corresponded to the phylogenic grouping in genotypes. We assembled a core set of 20 barley genotypes (~1/5 of original population size) to sustain sufficient mapping of SSR marker with Phenotype, in which we proposed four SSR markers, Bmac0040, Bmac0134, Bmag0125 and Bmag0211 for malt gene and marker (Bmac0399) for tolerance to salinity gene, which will be applicable for marker assisted breeding in barley gene resources.

Genome-wide characterization and functional analysis of class III peroxidase gene family in soybean reveal regulatory roles of GsPOD40 in drought tolerance.

Class III peroxidases (PODs) are plant-specific glycoproteins, that play essential roles in various plant physiological processes and defence responses. To date, scarce information is available about the POD gene family in soybean. Hence, the present study is the first comprehensive report about the genome-wide characterization of GmPOD gene family in soybean (Glycine max L.). Here, we identified a total of 124 GmPOD genes in soybean, that are unevenly distributed across the genome. Phylogenetic analysis classified them into six distinct sub-groups (A-F), with one soybean specific subgroup. Exon-intron and motif analysis suggested the existence of structural and functional diversity among the sub-groups. Duplication analysis identified 58 paralogous gene pairs; segmental duplication and positive/Darwinian selection were observed as the major factors involved in the evolution of GmPODs. Furthermore, RNA-seq analysis revealed that 23 out of a total 124 GmPODs showed differential expression between drought-tolerant and drought-sensitive genotypes under stress conditions; however, two of them (GmPOD40 and GmPOD42) revealed the maximum deregulation in all contrasting genotypes. Overexpression (OE) lines of GsPOD40 showed considerably higher drought tolerance compared to wild type (WT) plants under stress treatment. Moreover, the OE lines showed enhanced photosynthesis and enzymatic antioxidant activities under drought stress, resulting in alleviation of ROS induced oxidative damage. Hence, the GsPOD40 enhanced drought tolerance in soybean by regulating the key physiological and biochemical pathways involved in the defence response. Lastly, the results of our study will greatly assist in further functional characterization of GsPODs in plant growth and stress tolerance in soybean.

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.

TWIST1 is a transcription factor that is necessary for healthy neural crest migration, mesoderm development, and gastrulation. It functions as a key regulator of epithelial-to-mesenchymal transition (EMT), a process by which cells lose their polarity and gain the ability to migrate. EMT is often reactivated in cancers, where it is strongly associated with tumor cell invasion and metastasis. Early work on TWIST1 in adult tissues focused on its transcriptional targets and how EMT gave rise to metastatic cells. In recent years, the roles of TWIST1 and other EMT factors in cancer have expanded greatly as our understanding of tumor progression has advanced. TWIST1 and related factors are frequently tied to cancer cell stemness and changes in therapeutic responses and thus are now being viewed as attractive therapeutic targets. In this review, we highlight non-metastatic roles for TWIST1 and related EMT factors in cancer and other disorders, discuss recent findings in the areas of therapeutic resistance and stemness in cancer, and comment on the potential to target EMT for therapy. Further research into EMT will inform novel treatment combinations and strategies for advanced cancers and other diseases.

Incidence of aflatoxin M1 in cows' milk in Pakistan, effects on milk quality and evaluation of therapeutic management in dairy animals.

The present study was aimed at measuring the concentration of aflatoxin M1 (AFM1) in the milk of Holstein Friesian cows, its effect on the milk quality and seasonal trends, as well as to investigate the efficacy of a commercial clay-based toxin binder. For this purpose, milk samples from dairy cows (n = 72) were collected and assayed for AFM1 before employing a clay-based toxin binder. The milk samples (n = 72) were collected from selected animals, revealing that 69.4% of the milk samples had AFM1 levels above the United States permissible limit (0.5 µg/kg). The incidence of AFM1 in milk during the winter and summer was 82.5% and 53.1%, respectively. Owing to the presence of AFM1, the level of milk fat, solids-not-fat, and protein were found to be low. Subsequently, the affected animals were divided into two groups, i.e., AFM1 positive control (n = 10) and the experimental group (n = 40). The experimental group of animals were fed the clay-based toxin binder at 25 g/animal/day. A progressive decrease of 19.8% in the AFM1 levels was observed on day 4 and on day 7 (53.6%) in the treatment group. Furthermore, the fat, solids-non-fat and protein increased significantly in the milk. In conclusion, a high level of AFM1 contamination occurs in the milk in Pakistan, affecting the quality of the milk production. Clay-based toxin binders may be used to ensure the milk quality and to protect the animal and consumer health.

Seroprevalence and haemato-biochemical effects of bovine leucosis in buffalo, Punjab, Pakistan.

Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association (P < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.

Characteristics and comparative analysis of Mesona chinensis Benth chloroplast genome reveals DNA barcode regions for species identification.

Mesona chinensis Benth (MCB) is an important medicinal and edible plant in Southern China and Southeast Asian countries. Chloroplast (cp) genome is usually used for plant phylogeny, species identification, and chloroplast genetic engineering. To characterize the cp genome and determine the evolutionary position and perform the genetic diversity analysis of MCB, we sequence and characterize the MCB cp genome. The results show that the cp genome of MCB is a single circular molecule with a length of 152,635 bp. It is a typical quadripartite structure, comprising a large single-copy region (LSC, 83,514 bp) and a small single-copy region (SSC, 17,751 bp) separated by two inverted repeat regions (IRs, 51,370 bp). It encodes 129 unique genes, including 84 protein-coding genes (PCGs), 37 transfer RNAs (tRNAs), and 8 ribosomal RNAs (rRNAs). Altogether 127 simple sequence repeats (SSRs) are identified in the MCB cp genome with 86.61% of mononucleotide repeats. Phylogenetic analysis reveals that MCB is most closely related to Ocimum basilicum based on the whole cp genomes. Several highly divergent regions are found, such as trnH_psbA, rps16_trnQ, trnS_trnG, trnE_trnT, psaA_ycf3, rpl32_trnL, ccsA_ndhD, ndhG_ndhI, and rps15_ycf1, which can be proposed for use as DNA barcode regions. Genetic diversity analysis unveils a relatively narrow genetic basis of MCB germplasm resources. Therefore, the innovative breeding of MCB is very urgent and necessary in future research.

Holographic Manipulation of Nanostructured Fiber Optics Enables Spatially-Resolved, Reconfigurable Optical Control of Plasmonic Local Field Enhancement and SERS.

Integration of plasmonic structures on step-index optical fibers is attracting interest for both applications and fundamental studies. However, the possibility to dynamically control the coupling between the guided light fields and the plasmonic resonances is hindered by the turbidity of light propagation in multimode fibers (MMFs). This pivotal point strongly limits the range of studies that can benefit from nanostructured fiber optics. Fortunately, harnessing the interaction between plasmonic modes on the fiber tip and the full set of guided modes can bring this technology to a next generation progress. Here, the intrinsic wealth of information of guided modes is exploited to spatiotemporally control the plasmonic resonances of the coupled system. This concept is shown by employing dynamic phase modulation to structure both the response of plasmonic MMFs on the plasmonic facet and their response in the corresponding Fourier plane, achieving spatial selective field enhancement and direct control of the probe's work point in the dispersion diagram. Such a conceptual leap would transform the biomedical applications of holographic endoscopic imaging by integrating new sensing and manipulation capabilities.

Design of vanadium-dioxide-based resonant structures for tunable optical response.

Phase change materials are suitable for tunable photonic devices where the optical response can be altered under external stimuli, such as heat, an electrical or an optical signal. In this scenario, we performed numerical simulations to study the optical properties of a flat unpatterned resonant structure and a grating, both coated with a thin film of vanadium dioxide (VO2). Our results suggest that it is possible to modulate broadband and narrowband reflectance spectra of the resonant structures in the visible to near-infrared range by more than 40 % when the VO2 undergoes an insulator-to-metal phase transition. Resonant devices with a tunable spectral response may find application in sensors, filters, absorbers, and detectors.

Conditioning with melphalan 200 mg/m2 and subsequent ASCT improves progression-free and overall survival in elderly myeloma patients compared to standard of care.

OBJECTIVES: Despite the effectiveness of newer drugs for the treatment of multiple myeloma (MM), the outcomes are further improved by subsequent autologous stem cell transplantation (ASCT). Data on effectiveness in older patients are limited. We compared outcomes in patients aged 65-75 years depending on whether they were treated with ASCT or not and compared those to outcomes in patients <65 years. METHODS: This was a retrospective, single-center study. We compared progression-free survival (PFS) and overall survival (OS) for all MM patients below and above the age of 65 years treated ± ASCT at the Karolinska University Hospital between 2010 and 2020. PFS and OS were calculated by the Kaplan-Meier method. Variables affecting PFS and OS were evaluated using Cox regression model. RESULTS: Both PFS and OS were improved in the group 65-75 years treated +ASCT compared to those treated pharmacologically (p = 0.008 and p < 0.001, respectively). There were no significant differences between patients <65 years and those 65-75 years treated with ASCT. CONCLUSION: The findings indicate that even patients >65 years should be evaluated as candidates for ASCT. An individualized approach supported by a frailty/geriatric assessment score could assist clinicians to select the appropriate treatment for each patient.

Impact of COVID-19 on polio vaccination in Pakistan: a concise overview.

The pandemic of coronavirus disease 2019 (COVID-19) has disrupted immunization programs around the globe, potentially increasing life-threatening vaccine-preventable diseases. Pakistan and Afghanistan are the only countries, which are still struggling to eradicate wild poliovirus. All vaccination campaigns in Pakistan were suspended in April due to the COVID-19 outbreak, leading 40 million children to miss out on polio vaccination. Like the climate crisis, the COVID-19 pandemic could be regarded as a child-rights crisis because it could have life-threatening impact over children, who need immunization, now and in the long-term. Delays in polio vaccination programs might not have immediate impact but, in the long-term, the increase in polio cases in Pakistan could result in the global export of infections. Therefore, healthcare authorities must intensify their efforts to track and vaccinate unvaccinated children in countries like Pakistan and Afghanistan. Polio vaccination campaigns need to resume immediately, so we suggest applying social distancing measures along with standard operating procedure to flatten the transmission curve of COVID-19. Furthermore, the concurrent emergence of cVDPV2 means that tOPV should temporarily be used for primary immunization. In the current review, we have discussed delays in polio vaccination, surveillance of polio viruses, reported cases in Pakistan along with recommendations to overcome interrupted immunization.

Combined effects of virtual reality techniques and motor imagery on balance, motor function and activities of daily living in patients with Parkinson's disease: a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, impairing balance and motor function. Virtual reality (VR) and motor imagery (MI) are emerging techniques for rehabilitating people with PD. VR and MI combination have not been studied in PD patients. This study was conducted to investigate the combined effects of VR and MI techniques on the balance, motor function, and activities of daily living (ADLs) of patients with PD. METHODS: This study was a single-centered, two-armed, parallel-designed randomized controlled trial. A total of 44 patients of either gender who had idiopathic PD were randomly allocated into two groups using lottery methods. Both groups received Physical therapy (PT) treatment, while the experimental group (N: 20) received VR and MI in addition to PT. Both groups received assigned treatment for three days a week on alternate days for 12 weeks. The Unified Parkinson's Disease Rating Scale (UPDRS) (parts II and III), Berg Balance Scale (BBS), and Activities-specific Balance Confidence (ABC) Scale were used as outcome measures for motor function, balance, and ADLs. The baseline, 6th, and 12th weeks of treatment were assessed, with a 16th week follow-up to measure retention. The data was analysed using SPSS 24. RESULTS: The experimental group showed significant improvement in motor function than the control group on the UPDRS part III, with 32.45±3.98 vs. 31.86±4.62 before and 15.05±7.16 vs. 25.52±7.36 at 12-weeks, and a p-value < 0.001. At 12 weeks, the experimental group's BBS scores improved from 38.95±3.23 to 51.36±2.83, with p-value < 0.001. At 12 weeks, the experimental group's balance confidence improved considerably, from 59.26±5.87to 81.01±6.14, with a p-value of < 0.001. The experimental group's ADL scores improved as well, going from 22.00±4.64 to 13.07±4.005 after 12 weeks, with a p-value of < 0.001. CONCLUSION: VR with MI techniques in addition to routine PT significantly improved motor function, balance, and ADLs in PD patients compared to PT alone. TRIAL REGISTRATION: IRCT20200221046567N1 . Date of registration: 01/04/2020.