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Cardiovascular disease is the leading cause of death, medical complications, and healthcare costs. Although recent advances have been in treating cardiovascular disorders linked with a reduced ejection fraction, acutely decompensate cardiac failure remains a significant medical problem. The transient receptor potential cation channel (TRPC6) family responds to neurohormonal and mechanical stress, playing critical roles in cardiovascular diseases. Therefore, TRP C6 channels have great promise as therapeutic targets. Numerous studies have investigated the roles of TRP C6 channels in pain neurons, highlighting their significance in cardiovascular research. The TRPC6 protein exhibits a broad distribution in various organs and tissues, including the brain, nerves, heart, blood vessels, lungs, kidneys, gastrointestinal tract, and other bodily structures. Its activation can be triggered by alterations in osmotic pressure, mechanical stimulation, and diacylglycerol. Consequently, TRPC6 plays a significant role in the pathophysiological mechanisms underlying diverse diseases within living organisms. A recent study has indicated a strong correlation between the disorder known as TRPC6 and the development of cardiovascular diseases. Consequently, investigations into the association between TRPC6 and cardiovascular diseases have gained significant attention in the scientific community. This review explores the most recent developments in the recognition and characterization of TRPC6. Additionally, it considers the field's prospects while examining how TRPC6 might be altered and its clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study utilizes artificial intelligence and statistical modelling to optimize the operating parameters of a carbon-based electro-Fenton process for purifying model dye (RB19)-contaminated wastewater. Multilevel experimental Box-Behnken and uniform deisgns (BBD, UD) with four variables were analysed using polynomial regression analysis (PRA) and artificial neural networks (ANN), while the process optimisation was done using desirability function. For the given testing range but different design matrices and runs, both designs predicted a maximum RB19 removal (RB19-RR) of 90 ± 2.1% at lowest energy consumption (EC) of 0.44 ± 2.5 Wh, when voltage, Na 2 SO 4 , FeSO 4 , and time were maintained as follows: 4-5.3 V, 7-11 mM, 0.4-0.6 mM, and 35-40 min, respectively. All the design-model combinations portrayed the similar senitivity analyses, revealing that RB19 degradation and EC are primarily influenced by electrolysis time and voltage. The performance assessment demonstrated that all the design-model combinations also excellently predicted for unseen conditions as the maximum root mean squared error (RMSE) value for RB19-RR was 4.07, while it was 0.072 for EC, however, BBD-ANN performance proved to be slightly better than others. Having ∼57% less experimentation, UD based models managed to accurately predict the results for unseen conditions as the statistical errors were quite insignificant, even in some cases, RMSE found to be less for UD compared to BBD, elucidating the potential of uniform design as an alternative of conventional factorial designs. Nevertheless, the prediction accuracy is also dependent on modelling approach, as in some cases ANN failed to predict the response precisely specially when dealing with small data. Furthermore, techno-economic evaluation results spell out the efficacy of carbon felt based enhanced electro-Fenton process as promising environmental remediation technology and highlight its practical implication from view of operational cost., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The tumor microenvironment (TME), which includes both cellular and non-cellular elements, is now recognized as one of the major regulators of the development of primary tumors, the metastasis of which occurs to specific organs, and the response to therapy. Development of immunotherapy and targeted therapies have increased knowledge of cancer-related inflammation Since the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) limit immune cells from entering from the periphery, it has long been considered an immunological refuge. Thus, tumor cells that make their way "to the brain were believed to be protected from the body's normal mechanisms of monitoring and eliminating them. In this process, the microenvironment and tumor cells at different stages interact and depend on each other to form the basis of the evolution of tumor brain metastases. This paper focuses on the pathogenesis, microenvironmental changes, and new treatment methods of different types of brain metastases. Through the systematic review and summary from macro to micro, the occurrence and development rules and key driving factors of the disease are revealed, and the clinical precision medicine of brain metastases is comprehensively promoted. Recent research has shed light on the potential of TME-targeted and potential treatments for treating Brain metastases, and we'll use that knowledge to discuss the advantages and disadvantages of these approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khan, Khan, Sala, Khan, Ud Din, Khan, Hassan, Khan and Liu.)

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by either a marked decrease or a complete absence of megakaryocytes with the preservation of all other cell lines. To date, more than 60 cases of AATP have been reported in the literature. Due to the rarity of this disease, no standard treatment guidelines have been established, and therapy is based on a handful of case studies and expert opinions. Herein, we provide a comprehensive review of currently utilized therapeutic options for AATP.

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also in the macrophages that compose the tumor microenvironment. This supports the idea that LGMN is a pivotal protein in regulating tumor development, invasion, and dissemination. Targeting LGMN with siRNA or chemotherapeutic medicines and peptides can suppress cancer cell proliferation in culture and reduce tumor growth in vivo . Furthermore, legumain can be used as a marker for cancer detection and targeting due to its expression being significantly lower in normal cells compared to tumors or tumor-associated macrophages (TAMs). Tumor formation is influenced by aberrant expression of proteins and alterations in cellular architecture, but the tumor microenvironment is a crucial deciding factor. Legumain (LGMN) is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. Its precise biological mechanism encompasses a number of routes, including effects on tumor-associated macrophage and neovascular endothelium in the tumor microenvironment. The purpose of this work is to establish a rationale for thoroughly investigating the function of LGMN in the tumor microenvironment and discovering novel tumor early diagnosis markers and therapeutic targets by reviewing the function of LGMN in tumor genesis and progression and its relationship with tumor milieu., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khan, Khan, Khan, Ud Din, Khan, Khan and Liu.)

Rational design and synthesis of multifunctional electrocatalysts with high electrochemical activity and low cost are significantly important for new-generation lithium-sulfur (Li-S) batteries. Herein, N-doped FeP nanospheres decorated N doped carbon matrix is successfully synthesized by facile one-pot pyrolysis and in-situ phosphorization technique to mitigate the conversion kinetics and suppress the shuttle effect. The large specific surface area with mesopores can incorporate up to 81.5% sulfur, with the conductive carbon and nitrogen co-matrix providing Li + /e - passage and fastening the redox kinetics. The remarkable adsorption properties and the electrocatalytic activity through physical confinement and chemical immobilization is thoroughly verified. Consequently, the FeP/CN@S deliver a high reversible capacity of 1183 mAh g -1 at 0.1C compared to Co/P/CN@S (961 mAh g -1 ); whereas, at 1C, a negligible decay rate of 0.04% is observed for 1000 cycles, possessing outstanding cycling stability and rate capability. Hence, the cost-effective in-situ phosphorization strategy to synthesize FeP/CN@S as an efficient nanoreactor is constructive to be applied in Li-S batteries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Severe haemolytic anaemia is a rare complication of haemodialysis that is often difficult to recognize, especially when there are other potential differential diagnoses. Here, we present the case of 19-year-old man on haemodialysis who developed severe haemolytic anaemia while recovering from acute renal failure secondary to rhabdomyolysis. Other causes of haemolytic anaemia such as thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome were ruled out. As his blood counts were dropping on days following haemodialysis, haemolysis secondary to the mechanical sheering effect of the catheter was considered and his haemodialysis catheter was exchanged, which led to the resolution of anaemia., Learning Points: Haemodialysis-related haemolysis can be due to the mechanical sheering effect of the catheter/tubing, and overheating or contamination of the dialysate fluid.Most cases of catheter or faulty tubing-related haemolysis need a high level of suspicion for diagnosis and normally resolve with correction of the underlying mechanical issue.Due to the rarity of the phenomenon, it is very important to rule out other life-threatening causes of haemolytic anaemia, such as disseminated intravascular coagulation and thrombotic thrombocytopenic purpura., Competing Interests: Conflicts of Interests: The authors declare there are no competing interests., (© EFIM 2021.)

A 44-year-old woman with no significant medical history presented with a 3-week history of high-grade fevers, fatigue and shortness of breath. Laboratory investigation was significant for lymphopenia and thrombocytopenia which progressively worsened during her hospital stay, along with new-onset anaemia, and elevated ferritin, transaminase and triglycerides. A computerized tomography (CT) scan of the abdomen revealed retroperitoneal lymphadenopathy. A bone marrow biopsy confirmed the diagnosis of haemophagocytic lymphohistiocytosis (HLH). Extensive infectious work-up revealed high IgG titres for Bartonella henselae and Coxiella burnetii . Interestingly, the left supraclavicular node was negative for both microbes by polymerase chain reaction (PCR), but the biopsy revealed anaplastic large T-cell lymphoma., Learning Points: Haemophagocytic lymphohistiocytosis (HLH) is an important differential diagnosis to consider for fever of unknown origin in adults, especially in the setting of pancytopenia and hyperferritinaemia.Q fever resulting from Coxiella burnetii can cause HLH and is also postulated to increase the risk of lymphoma. Bartonella henselae infection can also trigger HLH, but the risk of lymphoma following infection by B. henselae is unknown., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Study Design: Prospective clinical study., Purpose: The present study aimed to examine the neurological recovery pattern in cervical spondylotic myelopathy (CSM) after anterior cervical decompression and compare it with the existing reports in the literature., Overview of Literature: Neurological recovery and regression of myelopathy symptoms is an important factor that determines the outcomes of surgical decompression. The present findings contribute to the literature on the pattern of neurological recovery and patient prognosis with respect to the resolution of myelopathy symptoms after surgery., Methods: This prospective study was conducted in Government Medical College in Jammu, North India between November 2012 and October 2014, a total of 30 consecutive patients with CSM were included and treated with anterior decompression and stabilization. They were prospectively followed up for 1 year and were evaluated for their neurological recovery pattern. The postoperative outcome was evaluated using the modified Japanese Orthopaedic Association (mJOA) score. The recovery rate was calculated using Hirabayashi's method. The JOA score was assessed before the operation and postoperatively at 1 week, 2 weeks, 1 month, 3 months, 4 months, 6 months, and 1 year., Results: The postoperative mJOA score was 0 in the 1st month, 12.90±3.57 in the 3rd month, 13.50±3.55 in the 4th month, 14.63±3.62 in the 6th month, and 14.9±3.24 at the final follow-up of 1 year. The average recovery rate during the 1st month followup was 0%, and that during the 3rd month follow-up was 12.91% with a range of 0%-50%. The average recovery rate during the 4th month was 32.5%, with a range of 0%-60%, while that during the 6th month was 72.83%, with a range of 0%-100%. The average recovery rate during the final follow-up of 1 year was 54.3%., Conclusions: Neurological recovery after surgical decompression starts from the 3rd postoperative month and progresses until the 6th postoperative month; thereafter, it gradually plateaus over the subsequent 6 months until it steadies. Symptom duration is an important factor that requires consideration while determining postoperative neurological recovery.

Designing a self-assembling structure for a Pt-based catalyst offers a great opportunity to enhance the electrocatalytic performance and maximize the use of precious metals. Herein, we report an etching method based on thermal treatment for the removal of less active metals from Pt-based alloys for the enhancement of the oxygen reduction reaction. PtPdAg nanostructures' self-assembly can be easily controlled to the dimer stage or nanowires by stirring the nanoparticles in formamide with or without potassium iodide under heat for specific times. Thus oxygen reduction reaction-favoring PtPdAg hollow nanoparticle, nanodimer and nanowire catalysts are synthesized, all of which have been demonstrated to be promoting factors for the ORR. In a Pt-based catalyst, the arrangement and configuration of the surface or topmost few layer atoms influence the adsorption of oxygen and activation for ORR. The PtPdAg dimer catalyst shows excellent ORR activity compared to other PtPdAg nanostructures and commercial Pt/C i.e. 7.2 times higher specific activity and 4.1 times higher mass activity. We further carried out DFT calculations and from the results, we conclude that the most chemically inequivalent structure such as PtPdAg/C nanodimer alloys possesses the weakest oxygen binding energy.

Two-dimensional nanomaterials, particularly multimetallic nanosheets with single or few atoms thickness, are attracting extensive research attention because they display remarkable advantages over their bulk counterparts, including high electron mobility, unsaturated surface coordination, a high aspect ratio, and distinctive physical, chemical, and electronic properties. In particular, their ultrathin thickness endows them with ultrahigh specific surface areas and a relatively high surface energy, making them highly favorable for surface active applications; for example, they have great potential for a broad range of fuel cell applications. First, the state-of-the-art research on the synthesis of nanosheets with a controlled size, thickness, shape, and composition is described and special emphasis is placed on the rational design of multimetallic nanosheets. Then, a correlation is performed with the performance of multimetallic nanosheets with modified and improved electrochemical properties and high stability, including for the oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), formic acid oxidation (FAO), methanol oxidation reaction (MOR), ethanol oxidation reaction (EOR), and methanol tolerance are outlined. Finally, some perspectives and advantages offered by this class of materials are highlighted for the development of highly efficient fuel cell electrocatalysts, featuring low cost, enhanced performance, and high stability, which are the key factors for accelerating the commercialization of future promising fuel cells.

A hierarchical excavated iron-nitrogen codoped mesoporous carbon (Ex-FeN-MC) electrocatalyst has been successfully synthesized by pyrolysis of the unique ureidopyrimidinone containing organic precursor MAMIS by using silica as the mesoporous template and iron nitrate as the source of iron. The selected organic precursor has multifunctionalities with diverse distribution of nitrogen and oxygen species which constitute interesting features to prepare the Ex-FeN-MC electrocatalyst. The as-prepared Ex-FeN-MC material shows unexpectedly higher catalytic activities towards ORR/OER performances with an overpotential of 250 mV for OER in alkaline solution at a current density of 10 mA cm -2 , while the ORR activity is almost similar to that of commercial Pt/C. It is believed that the excellent electrochemical performance results from the synergic contribution of the hierarchical uniform mesoporous structure, evenly distributed iron nanoparticles and high density of Ex-FeN-MC catalytically active sites. The presence of the hierarchical uniform mesoporous structure considerably accelerates the mass transfer and efficiently promotes the full utilization of active sites. Furthermore, it also possesses amorphous carbon in coexistence with lattice graphitic carbon which also enhanced the ORR/OER performances. Our research findings can surely provide a new insight to design highly active ORR/OER electrocatalysts by utilizing more novel organic precursors to provide interesting characteristics to electrocatalysts, as well as open up a route for constructing unique multifunctional materials with mesoporous architectures for electrocatalysis and supercapacitor applications.

Development of efficient electrocatalysts for oxygen evolution reaction (OER) is of great significance for future renewable energy applications. Herein, efficient OER electrocatalysts based on iron hydroxide-modified nickel hydroxylphosphate (NiPO/Fe(OH) x ) single-wall nanotubes (SWNTs) have been prepared by a facile stepwise surfactant-free solvothermal strategy, which possess diameters of about 6 nm and lengths of about several micrometers. Benefiting from the synergistic effect between iron hydroxides and NiPO SWNTs, the as-prepared NiPO/Fe(OH) x SWNTs exhibit higher OER activity than primary NiPO SWNTs. Furthermore, the OER activity with different Fe contents displays a volcano-type shape, and the optimized NiPO/Fe(OH) x SWNTs present excellent activity with a low overpotential of 248 mV to deliver a current density of 10 mA cm -2 and 323 mV to achieve a large current density of 100 mA cm -2 , as well as a remarkably low Tafel slope of 45.4 mV dec -1 in 1 M KOH electrolyte. The present work provides valuable insights to improve the OER performance by rational surface modification.

Ultrathin nanocrystals generally provide a remarkable catalytic performance due to their high specific surface area and exposure of certain active sites. However, deactivation caused by growth and gathering limits the catalytic application of ultrathin nanocrystals. Here we report Ag nanocrystal-decorated polyoxometalate (Ag-POM) single-walled nanotubes assembled via a concise, surfactant-free soaking method as a new kind of well-defined core-sheath nanoreactor. The diameter of Ag nanocrystals inside polyoxometalate nanotubes can be controlled via simply adjusting the reactant concentration. Ag-POM provided outstanding oxidative desulfurization (ODS) catalytic performance for aromatic sulfocompounds at room temperature. It was suggested that Ag nanocrystals decorated on the inner surface played a key role in adjusting the electronic distribution and enhancing the catalytic activity. The as-prepared Ag-POM nanotubes are promising candidate catalysts with enhanced performance for practical catalytic applications in the gasoline desulfurization industry.

Mechanistic control is a powerful means for manufacturing specific shapes of metal nanostructures and optimizing their performance in a variety of applications. Thus, we successfully synthesized multimetallic nanoplates (PtAgBiCo and PtAgBi) by combining the concepts of crystal symmetry, oxidative etching and seed ratio, and tuned their activity, stability and methanol tolerance, as well as Pt utilization, for the oxygen reduction reaction in direct methanol fuel cells. Systematic studies reveal that the formation of PtAgBiCo triangular nanoplates with a high morphological yield (>90%) can be achieved by crystallinity alteration, while electrochemical measurements indicate that the PtAgBiCo nanoplates have superior electrocatalytic activity towards the oxygen reduction reaction. The specific and mass activity of the PtAgBiCo nanoplates are 8 and 5 times greater than that of the commercial Pt/C catalyst, respectively. In addition, the tetrametallic PtAgBiCo nanoplates exhibit a more positive half-wave potential for the oxygen reduction reaction and possess an excellent methanol tolerance limit compared with the commercial Pt/C catalyst.

Porous PtCuBiMn nanosheets are developed with a thickness of ≈3-4 nm. The specific and mass activities of these nanosheets are ten and seven times greater than that of commercial Pt/C catalyst, respectively. PtCuBiMn nanosheets demonstrate superior catalytic performance for the oxygen reduction reaction, as well as resistance to methanol cross-over effects, suggesting that it is a promising catalyst for direct methanol fuel cells., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pakistan has a large population of more than 150 million people with an overall carrier frequency of approximately 5.6% for beta-thalassemia. Punjab is the largest province of the country having more than 50% of the population. The state of beta-thalassemia is alarming as consanguinity is very high (>81%) and the literacy rate is low in South Punjab. A thalassemia prevention program is the need of the hour in this part of Pakistan. In this study, we initiated awareness, screening, and characterization of the mutations causing beta-thalassemia as well as a genetic counseling program mainly in the districts of Faisalabad and D.G. Khan to establish prenatal diagnosis, a facility previously unavailable in this region for disease prevention. A total of 248 unrelated transfusion-dependent children and the available members of their families were screened to characterize the mutations and identify the carriers. Genetic counseling was provided to these families and prenatal diagnosis offered. In the samples analyzed, 11 beta-thalassemia mutations and three hemoglobin variants were detected mainly by using the Monoplex and Multiplex ARMS-PCR. First-trimester prenatal diagnosis was carried out through chorionic villus sampling (CVS) in seven pregnancies at risk. As a result of our campaign, 145 carrier couples planning to have more children gave their consent to have retrospective prenatal diagnosis in every pregnancy in future. A cooperative trend and a positive attitude toward the prevention of beta-thalassemia were noticed in the families with affected children and in the general population.

We present here an analysis of 888 unrelated beta-thal chromosomes consisting of 444 transfusion dependent children from various regions of Punjab and Islamabad Pakistan. By using Multiplex ARMS- PCR, restriction endonuclease analysis, allele specific oligonucleotide (ASO) hybridization and sequencing, 17 beta-thal mutations and 3 Hb variants were detected in 99.5 % (884/888) of the chromosomes analyzed. First trimester prenatal diagnosis by chorionic villus sampling (CVS) was also carried out in seven pregnancies at risk of beta-thalassemia. Our results indicate that three most common mutations accounted for 86.8% of the beta-thal alleles in this region. These findings have important implications for prevention of beta-thalassemia through genetic counseling and prenatal diagnosis in this part of Pakistan.

Objectives: To report a rare case of moyamoya syndrome with primary antiphospholipid syndrome (APS)., Clinical Presentation and Intervention: A 41-year-old woman was admitted with sudden onset of left-sided hemiparesis. Magnetic resonance imaging and magnetic resonance angiography of the brain showed characteristic features of moyamoya vessels. Laboratory investigations revealed raised levels of anticardiolipin antibody. She made a complete and uneventful recovery with aspirin and intensive physiotherapy over a period of 2 weeks., Conclusion: The association of APS and moyamoya disease may present a dilemma in management. While APS is often considered to be an indication for giving anticoagulation, a trial of antiplatelet agents is preferable to anticoagulation because of the risk of bleeding from the fragile moyamoya vessels., (Copyright 2006 S. Karger AG, Basel.)

Ectodermal dysplasia (ED) represents a heterogeneous group of genetic disorders characterized by the absence or deformity in two or more of the ectodermal appendages. We have studied an autosomal recessive form of ED in 13 individuals over six generations from an inbred Pakistani family. The clinical features of the affected individuals include highly dystrophic nails and thin hair on scalp, fine eyebrows and eyelashes, and thin body hair. Genome-wide linkage analysis of 390 microsatellite markers mapped the ED gene to the 3.92 cM interval flanked by markers D10S1710 and D10S1741 on chromosome 10q24.32-q25.1. Multipoint linkage analysis generated a maximum logarithm of odds ratio score of 4.79 in the interval D10S1239-D10S1264, which corresponds to 6.35 Mb.

Objective: To determine the efficacy and safety of transcatheter embolization of nonvariceal gastrointestinal hemorrhage., Design: Descriptive analytical study., Place and Duration of Study: Radiology Department, The Aga Khan University Hospital, Karachi, Pakistan, from October 1999 to August 2004., Subjects and Methods: The study included 27 patients who underwent angiography for suspected gastrointestinal hemorrhage. The presumptive diagnosis was based on the findings of endoscopy in 08 patients, scintigraphy in 05 patients and on clinical findings only in 14 patients. Nine patients had gastroduodenal hemorrhage, 04 patients had hemobilia and 14 patients had lower gastrointestinal bleeding. Five patients had comorbidities. One patient had uremia, 2 had hepatitis C, 1 had cirrhosis and 1 had coagulopathy. Technical success, clinical success, complications and patient survival were assessed., Results: Nine patients had upper gastrointestinal hemorrhage, 4 patients had hemobilia and 14 patients had lower gastrointestinal bleeding. Etiology of bleeding was known in 15 patients and unknown in 12 patients. Clinical success was achieved in 23 (85.18%) of 27 patients. Two patients had early rebleeding. One of these was managed surgically and recovered. The other had severe coagulopathy and was unfit for surgery. Two patients had bowel infarction, one of these was managed surgically and recovered and the other died of complication of procedure. One patient had small splenic infarcts and was managed conservatively. Overall 85.18% success was achieved for the embolization procedure. Two of 27 patients died. One patient died because of recurrence of bleeding and other died because of infarction of right hemi-colon which occurred as complication of embolization., Conclusion: Transcatheter embolization is effective and safe in patients with nonvariceal gastrointestinal hemorrhage.