A Bibliometric Analysis of the 100 Most-Cited Articles on Otoplasty.

A bibliometric analysis was conducted in April 2024 to review the current trends in otoplasty. It involved a literature search of the Scopus database for original articles with the query terms "otoplasty" and "pinnaplasty," without restricting publication dates or selecting journals in the database. The top 100 articles with the highest citations were reviewed. Bibliometric analysis was performed with the Scimago journal impact factor. The screening was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to extract the top 100 most-cited articles in otoplasty. We excluded articles not focused on otoplasty, those involving other surgical procedures, and non-English articles. With Scopus and manual screening, we performed citation analysis of selected articles. Mean values were calculated for the number of citations and citations per year. Of the 951 studies identified, 100 (10.5%) were analyzed in detail. The studies were published between 1941 and 2024, with a mean of 36 ± 23.7 citations per paper. The journal Plastic and Reconstructive Surgery reported the highest number (23%, n = 23) of articles, followed by the Journal of Plastic, Reconstructive and Aesthetic Surgery with 13% (n = 13) articles. The highest number of articles originated from the United States (38%, n = 38), followed by the United Kingdom (15%, n = 15). Our bibliometric analysis provides a comprehensive overview of the landscape of otoplasty research, highlighting key publications, authors, and journals. This study contributes to the understanding of the evolution and impact of otoplasty literature, laying the groundwork for further research and innovation in this field.

A Circular RNA Generated from Nebulin (NEB) Gene Splicing Promotes Skeletal Muscle Myogenesis in Cattle as Detected by a Multi-Omics Approach.

Cattle and the draught force provided by its skeletal muscle have been integral to agro-ecosystems of agricultural civilization for millennia. However, relatively little is known about the cattle muscle functional genomics (including protein coding genes, non-coding RNA, etc.). Circular RNAs (circRNAs), as a new class of non-coding RNAs, can be effectively translated into detectable peptides, which enlightened us on the importance of circRNAs in cattle muscle physiology function. Here, RNA-seq, Ribosome profiling (Ribo-seq), and peptidome data are integrated from cattle skeletal muscle, and detected five encoded peptides from circRNAs. It is further identified and functionally characterize a 907-amino acids muscle-specific peptide that is named circNEB-peptide because derived by the splicing of Nebulin (NEB) gene. This peptide localizes to the nucleus and cytoplasm and directly interacts with SKP1 and TPM1, key factors regulating physiological activities of myoblasts, via ubiquitination and myoblast fusion, respectively. The circNEB-peptide is found to promote myoblasts proliferation and differentiation in vitro, and induce muscle regeneration in vivo. These findings suggest circNEB-peptide is an important regulator of skeletal muscle regeneration and underscore the possibility that more encoding polypeptides derived by RNAs currently annotated as non-coding exist.

Multi-nodal basin drainage in lower limb melanoma.

Lymph node status is an important factor that influences outcomes in melanoma. Whilst certain anatomical areas have multiple-nodal basin drainage, limb melanomas are thought to have more predictable lymphatic drainage patterns, with lower limb melanomas reliably draining to the corresponding ipsilateral inguinal lymph node basin with occasional popliteal drainage. Here we share our unique experience of a patient with a lower limb melanoma demonstrating sentinel lymph nodes, and subsequent metastatic spread, in both the ipsilateral and contralateral inguinal lymph node basins, highlighting an important learning point with respect to our clinical examination of melanoma patients.

Genome-wide identification and evolutionary analysis of the FGF gene family in buffalo.

Fibroblast growth factors (FGFs) are important polypeptide growth factors that play a critical role in many developmental processes, including differentiation, cell proliferation, and migration in mammals. This study employs in silico analyses to characterize the FGF gene family in buffalo, investigating their genome-wide identification, physicochemical properties, and evolutionary patterns. For this purpose, genomic and proteomic sequences of buffalo, cattle, goat, and sheep were retrieved from NCBI database. We identified a total of 22 FGF genes in buffalo. Physicochemical properties observed through ProtParam tool showed notable features of these proteins including in-vitro instability, thermostability, hydrophilicity, and basic nature. Phylogenetic analysis grouped 22 identified genes into nine sub-families based on evolutionary relationships. Additionally, analysis of gene structure, motif patterns, and conserved domains using TBtools revealed the remarkable conservation of this gene family across selected species throughout the course of evolution. Comparative amino acid analysis performed through ClustalW demonstrated significant conservation between buffalo and cattle FGF proteins. Mutational analysis showed three non-synonymous mutations at positions R103 > G, P7 > L, and E98 > Q in FGF4, FGF6, and FGF19, respectively in buffalo. Duplication events revealed only one segmental duplication (FGF10/FGF22) in buffalo and two in cattle (FGF10/FGF22 and FGF13/FGF13-like) with Ka/Ks values <1 indicating purifying selection pressure for these duplications. Comparison of protein structures of buffalo, goat, and sheep exhibited more similarities in respective structures. In conclusion, our study highlights the conservation of the FGF gene family in buffalo during evolution. Furthermore, the identified non-synonymous mutations may have implications for the selection of animals with better performance.Communicated by Ramaswamy H. Sarma.

In silico analysis and experimental validation shows negative correlation between miR-1183 and cell cycle progression gene 1 expression in colorectal cancer.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by binding to the 3' untranslated regions (UTR) of target genes. Aberrant expression of miRNAs can lead to disease, including cancer. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Among several factors, differential expression of miRNA can have serious consequences on disease progression. This study was designed to computationally identify and experimentally verify strong miRNA candidates that could influence CRC progression. In silico analysis of publicly available gene expression microarray datasets revealed significant upregulation of miR-1183 in CRC. Comparison of mRNA microarray expression data with predicted miR-1183 targets led to the identification of cell cycle progression gene 1 (CCPG1) as strong, negatively correlated miR-1183 target. Expression analysis by means of quantitative PCR validated the inverse correlation between miR-1183 and CCPG1 in colorectal cancer tissues. CCPG1 indirectly modulates the cell cycle by interacting with the PH/DH domain of Dbs (Rho-specific guanine nucleotide exchange factor). Interestingly, the computational analysis also showed that miR-1183 is upregulated in liver and gastric cancer. This finding is notable as the liver and stomach are the primary metastatic sites for colorectal cancer and hepatocellular carcinoma respectively. This novel finding highlights the broader implications of miR-1183 dysregulation beyond primary CRC, potentially serving as a valuable prognostic marker and a therapeutic target for both primary and metastatic CRC.

Impact of corporate motives for sustainable sourcing: key moderating role of regulatory pressure.

Organizational decisions and their motivations are crucial for successfully implementing sustainable sourcing practices (SSP). Still, there is scant research on how SSPs are impacted by corporate motives (CM). To fill this research gap, we formed a three-tiered stakeholder theory (ST) based paradigm that accounts for the moderating impact of regulatory pressure (RP) while examining the relationship between different types of corporate motives (instrumental, relational, and moral) and SSP. Partial least squares structural equation modeling (PLS-SEM) was used to examine data collected from 248 respondents in the Pakistani manufacturing industry. The outputs of SEM disclosed that all CMs affect SSP. RP also confoundedly moderated these targeted relationships. Importance performance map analysis (IPMA) showed that regulatory pressure (0.319) and relational motives (67.38) are more important and perform better than all other exogenous variables. This study sheds light on corporate strategies and decision-making in multi ways. All dimensions of CM greatly enhance SSP directly and through RP, as RP firmly moderates these associations, indicating the relevance of ST. Finally, this empirical investigation ends with a framework of testable assertions and many future research endeavors on environmental sustainability.

Second-Line Antiretroviral Treatment Outcome in HIV-Infected Patients Coinfected with Tuberculosis in Pakistan.

Background: Tuberculosis (TB) coinfection in human immunodeficiency virus- (HIV-) infected patients is considered a risk of antiretroviral therapy (ART) failure. Coadministration of antitubercular therapy (ATT) with ART is another challenge for TB management. Objective: The study was aimed at investigating contributing factors affecting treatment outcomes in HIV-/TB-coinfected patients. Design: Cross-sectional. Setting. Samples were collected from the Pakistan Institute of Medical Sciences Hospital Islamabad. Subject and Methods. Clinicodemographic and immunovirological factors between the two groups were compared. The Student t-test and chi-square test were applied to compare outcome variables, and logistic regression was applied to determine the effect of TB on virological failure (VF). Main Outcome Measures. TB coinfection did not increase VF even in univariate (p = 0.974) and multivariate analysis at 6 and 12 months of 2nd-line ART start. ARV switching was significant (p = 0.033) in TB-coinfected patients. VF was significantly high in ATT-coadministered patients along with a viral load of ≥1000 (p = 0.000). Sample Size and Characteristics. We recruited seventy-four HIV patients on 2nd-line ART; 33 coinfected with TB were followed for at least 12 months. Conclusion: In HIV-/TB-coinfected patients, CD4 count, CD4 gain, and VF remained comparable to HIV patients with no TB infection. ATT significantly affects the treatment outcome, suggesting drug-to-drug interactions. These factors are important to revisit the therapeutic guidelines to maximize the benefit of dual therapy in resource-limited settings.

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.

Computer-Aided Early Melanoma Brain-Tumor Detection Using Deep-Learning Approach.

Brain tumors affect the normal functioning of the brain and if not treated in time these cancerous cells may affect the other tissues, blood vessels, and nerves surrounding these cells. Today, a large population worldwide is affected by the precarious disease of the brain tumor. Healthy tissues of the brain are suspected to be damaged because of tumors that become the most significant reason for a large number of deaths nowadays. Therefore, their early detection is necessary to prevent patients from unfortunate mishaps resulting in loss of lives. The manual detection of brain tumors is a challenging task due to discrepancies in appearance in terms of shape, size, nucleus, etc. As a result, an automatic system is required for the early detection of brain tumors. In this paper, the detection of tumors in brain cells is carried out using a deep convolutional neural network with stochastic gradient descent (SGD) optimization algorithm. The multi-classification of brain tumors is performed using the ResNet-50 model and evaluated on the public Kaggle brain-tumor dataset. The method achieved 99.82% and 99.5% training and testing accuracy, respectively. The experimental result indicates that the proposed model outperformed baseline methods, and provides a compelling reason to be applied to other diseases.

De Novo Transcriptome Dataset Generation of the Swamp Buffalo Brain and Non-Brain Tissues.

The sequenced data availability opened new horizons related to buffalo genetic control of economic traits and genomic diversity. The visceral organs (brain, liver, etc.) significantly involved in energy metabolism, docility, or social interactions. We performed swamp buffalo transcriptomic profiling of 24 different tissues (brain and non-brain) to identify novel transcripts and analyzed the differentially expressed genes (DEGs) of brain vs. non-brain tissues with their functional annotation. We obtained 178.57 Gb clean transcriptomic data with GC contents 52.77%, reference genome alignment 95.36%, exonic coverage 88.49%. Totally, 26363 mRNAs transcripts including 5574 novel genes were obtained. Further, 7194 transcripts were detected as DEGs by comparing brain vs. non-brain tissues group, of which 3,999 were upregulated and 3,195 downregulated. These DEGs were functionally associated with cellular metabolic activities, signal transduction, cytoprotection, and structural and binding activities. The related functional pathways included cancer pathway, PI3k-Akt signaling, axon guidance, JAK-STAT signaling, basic cellular metabolism, thermogenesis, and oxidative phosphorylation. Our study provides an in-depth understanding of swamp buffalo transcriptomic data including DEGs potentially involved in basic cellular activities and development that helped to maintain their working capacity and social interaction with humans, and also, helpful to disclose the genetic architecture of different phenotypic traits and their gene expression regulation.

Cellular Prion Protein Role in Cancer Biology: Is It A Potential Therapeutic Target?

Cancers are worldwide health concerns, whether they are sporadic or hereditary. The fundamental mechanism that causes somatic or oncogenic mutations and ultimately aids cancer development is still unknown. However, mammalian cells with protein-only somatic inheritance may also contribute to cancerous malignancies. Emerging data from a recent study show that prion-like proteins and prions (PrPC) are crucial entities that have a functional role in developing neurological disorders and cancer. Furthermore, excessive PrPC expression profiling has also been detected in non-neuronal tissues, such as the lymphoid cells, kidney, GIT, lung, muscle, and mammary glands. PrPC expression is strongly linked with the proliferation and metastasis of pancreatic, prostate, colorectal, and breast malignancies. Similarly, experimental investigation presented that the PrPC expression, including the prion protein-coding gene (PRNP) and p53 ag are directly associated with tumorigenicity and metastasis (tumor suppressor gene). The ERK2 (extracellular signal-regulated kinase) pathway also confers a robust metastatic capability for PrPC-induced epithelial to mesenchymal transition. Additionally, prions could alter the epigenetic regulation of genes and overactive the mitogen-activated protein kinase (MAPK) signaling pathway, which promotes the development of cancer in humans. Protein overexpression or suppression caused by a prion and prion-like proteins has also been linked to oncogenesis and metastasis. Meanwhile, additional studies have discovered resistance to therapeutic targets, highlighting the significance of protein expression levels as potential diagnostic indicators and therapeutic targets.

pH-responsive albumin-coated biopolymeric nanoparticles with lapatinab for targeted breast cancer therapy.

One can enhance the therapeutic index of anti-cancer drugs using albumin as a tumor homing agent for targeted cancer therapy. Herein, we sought to load lapatinib (LAPA) into small albumin-coated biopolymeric (poly-lactic co-glycolic acid (PLGA)) nanoparticles (APL NPs) by an emulsification method to improve the anti-tumor efficacy of lapatinib. The prepared APL NPs exhibited a small spherical core with an average diameter of 120.5 ± 10.2 nm with a narrow particle size distribution, high drug loading capacity (LC of 9.65 ± 1.53 %), good entrapment efficiency (EE of 75.55 ± 3.25 %), enhanced colloidal stability and a pH-responsive controlled drug release profile. Their cell-uptake and cancer cell growth inhibition were significantly higher compared to free LAPA and uncoated PLGA-LAPA (UPL) NPs, most likely because aggressive breast tumor cells over-express albumin receptors and utilize albumin as nutrient source for their growth. In addition, APL NPs possessed enhanced tumor accumulation and prolonged blood residence time compared to free LAPA and UPL NPs, allowing for potent tumor growth inhibition while exhibiting excellent biosafety. In short, the current study exploited a new and simple strategy to concurrently improve the safety and efficacy of LAPA for breast cancer treatment.

Global data analysis and risk factors associated with morbidity and mortality of COVID-19.

This review was focused on global data analysis and risk factors associated with morbidity and mortality of coronavirus disease 2019 from different countries, including Bangladesh, Brazil, China, Central Eastern Europe, Egypt, India, Iran, Pakistan, and South Asia, Africa, Turkey and UAE. Male showed higher confirmed and death cases compared to females in most of the countries. In addition, the case fatality ratio (CFR) for males was higher than for females. This gender variation in COVID-19 cases may be due to males' cultural activities, but similar variations in the number of COVID-19 affected males and females globally. Variations in the immune system can illustrate this divergent risk comparatively higher in males than females. The female immune system may have an edge to detect pathogens slightly earlier. In addition, women show comparatively higher innate and adaptive immune responses than men, which might be explained by the high density of immune-related genes in the X chromosome. Furthermore, SARS-CoV-2 viruses use angiotensin-converting enzyme 2 (ACE2) to enter the host cell, and men contain higher ACE2 than females. Therefore, males may be more vulnerable to COVID-19 than females. In addition, smoking habit also makes men susceptible to COVID-19. Considering the age-wise distribution, children and older adults were less infected than other age groups and the death rate. On the contrary, more death in the older group may be associated with less immune system function. In addition, most of these group have comorbidities like diabetes, high pressure, low lungs and kidney function, and other chronic diseases. Due to the substantial economic losses and the numerous infected people and deaths, research examining the features of the COVID-19 epidemic is essential to gain insight into mitigating its impact in the future and preparedness for any future epidemics.

Comparative Genomic Characterization of Buffalo Fibronectin Type III Domain Proteins: Exploring the Novel Role of FNDC5/Irisin as a Ligand of Gonadal Receptors.

FN-III proteins are widely distributed in mammals and are usually involved in cellular growth, differentiation, and adhesion. The FNDC5/irisin regulates energy metabolism and is present in different tissues (liver, brain, etc.). The present study aimed to investigate the physiochemical characteristics and the evolution of FN-III proteins and FNDC5/irisin as a ligand targeting the gonadal receptors including androgen (AR), DDB1 and CUL4 associated factor 6 (DCAF6), estrogen-related receptor ß (ERR-ß), estrogen-related receptor γ (ERR-γ), Krüppel-like factor 15 (KLF15), and nuclear receptor subfamily 3 group C member 1 (NR3C1). Moreover, the putative role of irisin in folliculogenesis and spermatogenesis was also elucidated. We presented the molecular structure and function of 29 FN-III genes widely distributed in the buffalo genome. Phylogenetic analysis, motif, and conserved domain pattern demonstrated the evolutionary well-conserved nature of FN-III proteins with a variety of stable to unstable, hydrophobic to hydrophilic, and thermostable to thermo-unstable properties. The comparative structural configuration of FNDC5 revealed amino acid variations but still the FNDC5 structure of humans, buffalo, and cattle was quite similar to each other. For the first time, we predicted the binding scores and interface residues of FNDC5/irisin as a ligand for six representative receptors having a functional role in energy homeostasis, and a significant involvement in folliculogenesis and spermatogenesis in buffalo.

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders.

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

Molecular detection and characterization of ovine herpesvirus-2 using heminested PCR in Pakistan.

BACKGROUND: Malignant catarrhal fever (MCF) is a highly fatal lymphoproliferative disease of cattle, deer, bison, water buffalo, and pigs caused by the gamma-herpesviruses alcelaphine herpesvirus-1 (AlHV-1) and ovine herpesvirus-2 (OvHV-2). OBJECTIVES: This study aimed to determine the prevalence of OvHV-2 in sheep, goats, cattle, and buffalo in Rawalpindi and Islamabad, Pakistan, by applying molecular and phylogenetic methods. METHODS: Blood samples were aspirated from sheep (n = 54), goat (n = 50), cattle (n = 46) and buffalo (n= 50) at a slaughterhouse and several farms. The samples were subjected to heminested polymerase chain reaction (PCR), followed by sequencing and phylogenetic analysis of the OvHV-2 POL gene and the OvHV-2 ORF75 tegument protein gene. RESULTS: The highest percentage of MCF positive samples was in sheep (13%), whereas goat, cattle, and buffalo had lower positive percentages, 11%, 9%, and 6.5%, respectively. Four OvHV-2-positive PCR products obtained from sheep samples were sequenced. The sequences obtained were submitted to the NCBI GenBank database (MK852173 for the POL gene; MK840962, MK852171, and MK852172 for the ORF75 tegument protein gene). Phylogenetic analysis revealed a close similarity of study sequences with those of worldwide samples. CONCLUSIONS: This study is the first cross-sectional study on the prevalence and molecular detection of OvHV-2 in apparently healthy cattle and buffalo that could be carrying OvHV-2 acquired from OvHV-2-positive sheep and goats. The results indicate that OvHV-2 is circulating in Pakistan. Further studies are needed to characterize OvHV-2 and elucidate further its prevalence.

Appraisal of iron accumulation in soil, forages, and blood plasma of sheep and goats: a case study in different districts of Punjab, Pakistan.

Minerals are essential for ruminants affecting significantly the production of grazing livestock. Iron level in forages, soil, and blood plasma of the small ruminants (goat and sheep) was investigated in three districts of Punjab. Atomic absorption spectrophotometer was used to determine the concentration of iron in collected samples. The results revealed that the mean Fe concentrations in soil of districts Sargodha, Mianwali, and Bhakhar were significantly varied and ranged from 21.85 to 23.78, 28.45 to 31.2, and 18.079 to 24.33 mg/kg, respectively. The Fe level in soil of Mianwali significantly varied and was higher than Sargodha and Bhakkar. The mean Fe concentration in forages which were used for feeding purpose were significantly varied and found between 10.95-14.49, 23.63-25.65, and 6.616-9.45 mg/kg for Sargodha, Mianwali, and Bhakhar, respectively. The mean Fe concentrations in blood plasma of goat which consumed the contaminated forages were 8.5026-11.763 mg/L in district Sargodha, 19.77-20.19 mg/L in Mianwali, and 5.508-5.858mg/L in Bhakkar. In blood plasma of sheep, the residual levels of Fe in districts Sargodha, Mianwali, and Bhakhar were ranged from 9.987 to 12.455, 15.8 to 19.785, and 3.425 to 6.383 mg/L, respectively. This study provides the data of metals effected by different sites and also their mobility from low to higher trophic level which enables us to study the iron toxicity in different trophic levels, and we recommend different safe limits and treatment in case of low and high metal profile.

Genomic Identification, Evolution and Sequence Analysis of the Heat-Shock Protein Gene Family in Buffalo.

Heat-shock proteins (HSP) are conserved chaperones crucial for protein degradation, maturation, and refolding. These adenosine triphosphate dependent chaperones were classified based on their molecular mass that ranges between 10-100 kDA, including; HSP10, HSP40, HSP70, HSP90, HSPB1, HSPD, and HSPH1 family. HSPs are essential for cellular responses and imperative for protein homeostasis and survival under stress conditions. This study performed a computational analysis of the HSP protein family to better understand these proteins at the molecular level. Physiochemical properties, multiple sequence alignment, and phylogenetic analysis were performed for 64 HSP genes in the Bubalus bubalis genome. Four genes were identified as belonging to the HSP90 family, 10 to HSP70, 39 to HSP40, 8 to HSPB, one for each HSPD, HSPH1, and HSP10, respectively. The aliphatic index was higher for HSP90 and HSP70 as compared to the HSP40 family, indicating their greater thermostability. Grand Average of hydropathicity Index values indicated the hydrophilic nature of HSP90, HSP70, and HSP40. Multiple sequence alignment indicated the presence of highly conserved consensus sequences that are plausibly significant for the preservation of structural integrity of proteins. In addition, this study has expanded our current knowledge concerning the genetic diversity and phylogenetic relatedness of HSPs of buffalo with other mammalian species. The phylogenetic tree revealed that buffalo is more closely related to Capra hircus and distantly associated with Danio rerio. Our findings provide an understanding of HSPs in buffalo at the molecular level for the first time. This study highlights functionally important HSPs and indicates the need for further investigations to better understand the role and mechanism of HSPs.

Sorbicillinoid Derivatives From Sponge-Derived Fungus Trichoderma reesei (HN-2016-018).

Six new sorbicillinoids, trichoreeseione A (1) and B (2), trichodermolide B (3), 13-hydroxy-trichodermolide (4), 24-hydroxy-trichodimerol (5), 15-hydroxy-bisvertinol (7), together with three known analogs, trichodimerol (6), 24-hydroxy-bisvertinol (8), and bisvertinol (9), were isolated from the sponge-derived fungus Trichoderma reesei (HN-2016-018). Their structures including absolute configurations were elucidated by analysis of NMR, MS data, and calculated ECD spectra. Compounds 1 and 2 with a characteristic naphthalene-trione ring were firstly reported in sorbicillinoid family. Compounds 3 and 4 were two rare sorbicillinoids containing a unique bicycle [3.2.1] lactone skeleton, while 3 with a propan-2-one moiety was also recorded first time in this family. Compound 5 displayed cytotoxic activity against A549, MCF-7, and HCT116 cell lines with the IC50 values of 5.1, 9.5, and 13.7 µM, respectively.

Novel Targeted Therapies for Chronic Lymphocytic Leukemia in Elderly Patients: A Systematic Review.

Chronic lymphocytic leukemia (CLL) typically affects older patients; administration of traditional cytotoxic therapies in old patients has very modest benefit with no survival improvement. With better understanding of CLL biology, trends are shifting towards the use of targeted therapies. The objective of this article is to review the safety and efficacy of various novel agents that specifically target the dysregulated pathways, with particular attention to elderly patients. Agents like B-cell receptor (BCR) inhibitors (Bruton's tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.