Flexible and Convergent Enantioselective Total Synthesis of (R)-Juglanaloids A and B: Two Phthalide Spiro Alkaloids with Potential Alzheimer's Disease Inhibitory Activity.

Juglanaloids A and B are recently isolated natural products characterized by an unprecedented spiro bicyclic isobenzofuranone-tetrahydrobenzazepinone framework and a promising antiamyloid activity. Here reported is a straightforward convergent total synthesis of these natural products, which were obtained in high enantiomeric purity (94% and >99% ee for juglanaloids A and B, respectively) through an eight-step longest linear sequence, based on an efficient and reliable enantioselective phase-transfer-catalyzed alkylation step. Considering the interesting biological activity of juglanaloids, this convenient, highly enantioselective, flexible, and predictable synthetic strategy promises to be a powerful tool for accessing potentially bioactive spiro bicyclic phthalide-tetrahydrobenzazepinone derivatives.

Liver-boosting potential: chicory compound-mediated silver nanoparticles for hepatoprotection-biochemical and histopathological insights.

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20 mg/kg of body weight), fourth group (CCl4+chicory) (1.75 mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35 mg/kg), sixth group (CCl4 + chicory of 3.25 mg/kg), seventh group (CCl4 +AgNPs 1.75 mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35 mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25 mg/kg of b. wt.). Blood samples were taken 24 h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25 mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

Exposure to zinc oxide nanoparticles induced reproductive toxicities in male Sprague Dawley rats.

BACKGROUND: This research delves into the reproductive toxicology of zinc oxide nanoparticles (ZnO-NPs) in male Sprague Dawley rats. It specifically examines the repercussions of Zn accumulation in the testes, alterations in testosterone levels, and histopathological changes in the gonadal tissues. AIMS: The primary objective of this study is to elucidate the extent of reproductive toxicity induced by ZnO-NPs in male Sprague Dawley rats. The investigation aims to contribute to a deeper understanding of the potential endocrine and reproductive disruptions caused by ZnO-NPs exposure. METHODS: Characterization techniques including SEM-EDX and XRD affirmed the characteristic nature of ZnO-NPs. Twenty-five healthy post weaning rats (200-250 g) were intraperitoneally exposed to different concentrations of ZnO-NPs @ 10 or 20 or 30 mg/kg BW for 28 days on alternate days. RESULTS: Results showed significant dose dependent decline in the body weight and testicular somatic index of rats. It also showed significant dose dependent accumulation of Zn in testis with increasing dose of ZnO-NPs. Conversely, serum testosterone level and sperm count were reduced with increasing dose of ZnO-NPs. Histological results showed dose dependent abnormalities i.e., vacuolization, edema, hemorrhage, destruction of seminiferous tubules, loss of germ cells and necrosis in rat testis. CONCLUSION: The findings of this study clearly indicate that high doses of zinc oxide nanoparticles (ZnO-NPs) can adversely affect the structural integrity and functional efficacy of the male reproductive system. Given these results, it becomes crucial to implement stringent precautionary measures in the utilization of ZnO-NPs, particularly in cosmetics and other relevant sectors. Such measures are imperative to mitigate the toxicological impact of ZnO-NPs on the male reproductive system and potentially on other related physiological functions. This study underscores the need for regulatory vigilance and safety assessments in the application of nanotechnology to safeguard human health.

Analysis of two layered peristaltic-ciliary transport of Jeffrey fluid and in vitro preimplantation embryo development.

The analysis of peristaltic-ciliary transport in the human female fallopian tube, specifically in relation to the growing embryo, is a matter of considerable physiological importance. This paper proposes a biomechanical model that incorporates a finite permeable tube consisting of two layers, where the Jeffrey fluid model characterizes the viscoelastic properties of the growing embryo and continuously secreting fluid. Jeffrey fluid entering with some negative pressure gradient forms the core fluid layer while continuously secreting Jeffrey fluid forms the peripheral fluid layer. The resulting partial differential equations are solved for closed-form solutions after employing the assumption of long wavelength. The analysis delineated that increasing the constant secretion velocity, Darcy number, and Reynolds number leads to a decrease in the appropriate residue time of the core fluid layer and a reduction in the size of the secreting fluid bolus in the peripheral fluid layer. Eventually, the boluses completely disappear when the constant secretion velocity exceeds 3.0 Progesterone ([Formula: see text]) and estradiol ([Formula: see text]) directly regulate the transportation of the growing embryo, while luteinizing hormone (LH) and follicle-stimulating hormone (FSH), prolactin, anti-mullerian hormone (AMH), and thyroid-stimulating hormone (TSH) have an indirect effects. Based on the number and size of blastomeres, the percentage of fragmentation, and the presence of multinucleated blastomeres two groups were formed in an in vitro experiment. Out of 50 patients, 26 (76.5%) were pregnant in a group of the good quality embryos, and only 8 (23.5%) were in a group of the bad quality embryos. The transport of growing embryo in the human fallopian tube and preimplantation development of human embryos in in vitro are constraint by baseline hormones FSH, LH, prolactin, [Formula: see text], AMH, and TSH.

Struvite separation from wastewater and its use with sulfur-oxidizing bacteria improves phosphorus utilization in alkaline soil.

A major portion of phosphatic fertilizer comes from the limiting natural resource, rock phosphate, which demands a timely alternative. Struvite, a crystalline mineral of low solubility, is a worthwhile alternative. Evaluation of the local wastewater streams for their ability to precipitate struvite and its capability as phosphatic fertilizer under an alkaline soil environment was studied. Two stirring speeds, a pH range of 8.0-11.0, and a constant molar ratio were used to optimize local wastewater streams for struvite precipitation. Struvite was used in five different combinations to assess the release of phosphorus (P), including control (no P source), single superphosphate, struvite, struvite + sulfur, and rock phosphate with or without inoculation of sulfur-oxidizing bacteria (SOB). For struvite precipitation, low stirring speeds are ideal because the precipitates readily sink to the bottom once they form. Furthermore, the amalgamation of SOB with sulfur significantly improved P use efficiency under alkaline soils through increased phosphorus sources solubility and enabled optimum wheat production due to its low solubility in an alkaline soil condition. Due to its capacity to recycle phosphorus from wastewater, struvite is poised to emerge as a sustainable fertilizer and had an opportunity to capture a share of this expanding market.

Advances in Computational Intelligence Techniques-Based Multi-Intersection Querying Theory for Efficient QoS in the Next Generation Internet of Things.

An environment of physically linked, technologically networked things that can be found online is known as the "Internet of Things." With the use of various devices connected to a network that allows data transfer between these devices, this includes the creation of intelligent communications and computational environments, such as intelligent homes, smart transportation systems, and intelligent FinTech. A variety of learning and optimization methods form the foundation of computational intelligence. Therefore, including new learning techniques such as opposition-based learning, optimization strategies, and reinforcement learning is the key growing trend for the next generation of IoT applications. In this study, a collaborative control system based on multiagent reinforcement learning with intelligent sensors for variable-guidance sections at various junctions is proposed. In the future generation of Internet of Things (IoT) applications, this study provides a multi-intersection variable steering lane-appropriate control approach that uses intelligent sensors to reduce traffic congestion at many junctions. Since the multi-intersection scene's complicated traffic flow cannot be accommodated by the conventional variable steering lane management approach. The priority experience replay algorithm is also included to improve the efficiency of the transition sequence's use in the experience replay pool and speed up the algorithm's convergence for effective quality of service in the upcoming IoT applications. The experimental investigation demonstrates that the multi-intersection variable steering lane with intelligent sensors is an appropriate control mechanism, successfully reducing queue length and delay time. The effectiveness of waiting times and other indicators is superior to that of other control methods, which efficiently coordinate the strategy switching of variable steerable lanes and enhance the traffic capacity of the road network under multiple intersections for effective quality of service in the upcoming IoT applications.

Bismuth-Rich Co/Ni Bimetallic Metal-Organic Frameworks as Photocatalysts toward Efficient Removal of Organic Contaminants under Environmental Conditions.

Active photocatalysts with an efficiency of 99% were prepared for the degradation of the industrial dye, methylene blue (MB), under visible light irradiation. These photocatalysts comprised Co/Ni-metal-organic frameworks (MOFs), to which bismuth oxyiodide (BiOI) was added as a filler to prepare Co/Ni-MOF@BiOI composites. The composites exhibited remarkable photocatalytic degradation of MB in aqueous solutions. The effects of various parameters, including the pH, reaction time, catalyst dose, and MB concentration, on the photocatalytic activity of the prepared catalysts were also evaluated. We believe that these composites are promising photocatalysts for the removal of MB from aqueous solutions under visible light.

A Reversible Cause of Cutaneous Rash in a Patient With Alcohol Consumption.

The most common cutaneous manifestations of alcoholism include urticarial reaction, flushing, porphyria cutanea tarda, psoriasis, rosacea, seborrheic dermatitis, and pruritus. Here, we present a case of a young male with a history of alcohol abuse who presented with non-blanching, petechial, and perifollicular macular rash secondary to vitamin C deficiency in view of poor oral intake. The rash improved significantly with vitamin C supplementation. Although rare in developed countries, clinicians should keep vitamin C deficiency as a differential diagnosis for skin rash in alcohol consumers.

Omadacycline for the treatment of Mycobacterium abscessus infections: Case series and review of the literature.

Treatment of Mycobacterium abscessus infections are problematic due to inherent multidrug resistance and lack of response to antibacterials commonly used as therapy for other mycobacterial infections. We report the clinical success of five patients who received definitive-treatment with an omadacycline-containing combination regimen for M. abscessus infection.

Co-occurrence of CML Blast Crisis and Severe COVID 19 Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affecting multiple organ systems. It can cause severe cytokine storms leading to intensive care unit admission requiring mechanical ventilation. However, there have been few studies establishing the outcomes of chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors who are infected with COVID-19. We present a 69-year-old male with a history of CML on imatinib therapy with COVID-19 who developed acute respiratory distress syndrome needing mechanical ventilatory support, shock requiring vasopressors, and worse outcome secondary to blast crisis.

Synthesis of Functionalized N-(4-Bromophenyl)furan-2-carboxamides via Suzuki-Miyaura Cross-Coupling: Anti-Bacterial Activities against Clinically Isolated Drug Resistant A. baumannii, K. pneumoniae, E. cloacae and MRSA and Its Validation via a Computational Approach.

N-(4-bromophenyl)furan-2-carboxamide (3) was synthesized by the reaction furan-2-carbonyl chloride (1) and 4-bromoaniline (2) in the presence of Et3N in excellent yields of 94%. The carboxamide (3) was arylated by employing triphenylphosphine palladium as a catalyst and K3PO4 as a base to afford N-(4-bromophenyl)furan-2-carboxamide analogues (5a-i) in moderate to good yields (43-83%). Furthermore, we investigated the in vitro anti-bacterial activities of the respective compounds against clinically isolated drug-resistant bacteria A. baumannii, K. pneumoniae, E. cloacae and S. aureus. The molecule (3) was found to be the most effective activity against these bacteria, particularly NDM-positive bacteria A. baumannii as compared to various commercially available drugs. Docking studies and MD simulations further validated it, expressing the active site and molecular interaction stability.

A Case of Idiopathic Cold Agglutinin Hemolytic Anemia Successfully Treated With Steroids.

Cold agglutinin disease (CAD) is a type of hemolytic anemia in which cold agglutinins can cause agglutination of red blood cells in cold parts of the body and hemolytic anemia. Cold agglutinin-mediated hemolytic anemia can occur in the setting of an underlying viral infection, autoimmune disorder, or lymphoid malignancy, referred to as a secondary cold agglutinin syndrome, or without one of these underlying disorders, referred to as primary CAD (also known as idiopathic CAD). We present a case of a 71-year-old female with hemolytic anemia due to primary CAD. The secondary causes of CAD, including infections, autoimmune disorders, and malignancy, were ruled out. She was successfully treated with prednisone.

Knowledge of Neural Tube Defects and Prevention Through Folic Acid Use Among Women in Faisalabad, Punjab, Pakistan: A Cross-Sectional Survey.

Objective: Neural tube defects (NTDs) are one of the most common congenital abnormalities of the central nervous system and are associated with significant mortality, morbidity, and major life-long disability. Periconceptional folic acid reduces the risk of NTDs by up to 70%; however, in Pakistan, no public information program exists concerning the risks of NTDs or promoting folic acid use. As such, the aim of this study was to assess levels of knowledge about NTDs and folic acid use among women attending the gynaecology department of DHQ Hospital, Faisalabad, Pakistan. Design: A cross-sectional survey. Setting: The gynaecology department of the District Head Quarter (DHQ) Hospital in Faisalabad, Pakistan. Participants: Three hundred and fifty-five married women. Primary and Secondary Outcome Measures: Primary outcome measures included knowledge of NTDs and knowledge of folic acid use. Results: About 85.4% of participants had no knowledge of neural tube defects and 76.7% reported no knowledge about folic acid use. The majority of participants (86.2%) were unaware that folic acid protects against NTDs. Lack of knowledge of NTDs was significantly associated with education (P = 0.001), husband's education (P = 0.002), planned pregnancy (P = 0.002), sources of antenatal care (P = 0.003), knowledge of folic acid (P = 003), knowledge that folic acid protects against NTDs (P = 0.002), and health decision-making (P = 0.003). Knowledge of folic acid use was significantly associated with age (P = 0.000), education (P = 0.004), husband's education (P = 0.002), monthly income (P = 0.003), planned pregnancy (P = 0.003), pregnancy trimester (P < 0.001), sources of antenatal care (P < 0.001), knowledge of NTDs (P = 0.002), knowledge that folic acid protects against NTDs (P < 0.001), use of folic acid (P < 0.001), sources of vitamin information (P < 0.001), and health decision-making (P = 0.002). Conclusion: These findings highlight extremely low levels of knowledge about NTDs and folic acid use of women in Pakistan. There is an urgent need to increase knowledge and awareness of the risks of NTDs and preventative approaches, through health education programs delivered by trusted health professionals.

Development of high temperature simultaneous saccharification and fermentation by thermosensitive Saccharomyces cerevisiae and Bacillus amyloliquefaciens.

Scarcity of energy and pollution are two major challenges that have become a threat to all living things worldwide. Bioethanol is a renewable, ecological-friendly clean energy that may be utilized to address these issues. This study aimed to develop simultaneous saccharification and fermentation (SSF) process through high temperature-substrate adaptation and co-cultivation of S. cerevisiae with other potential amylolytic strains. In this study, we adapted our previously screened thermosensitive Saccharomyces cerevisiae Dj-3 strain up-to 42 °C and also screened three potential thermotolerant amylolytic strains based on their starch utilization capability. We performed SSF fermentation at high temperature by adapted Dj-3 and amylolytic strains using 10.0% starch feedstock. Interestingly, we observed significant ethanol concentration [3.86% (v/v)] from high temperature simultaneous saccharification and fermentation (HSSF) of adapted Bacillus amyloliquefaciens (C-7) and Dj-3. We attribute the significant ethanol concentration from starch of this HSSF process to C-7's high levels of glucoamylase activity (4.01 U/ml/min) after adaptation in starch (up-to 42 °C) as well as Dj-3's strong glucose fermentation capacity and also their ethanol stress tolerance capability. This study suggests the significant feasibility of our HSSF process.

Dysbiosis in salivary bacterial diversity of postpartum females and its association with oral health problems and APOs.

The present study investigates the dysbiosis in salivary bacterial diversity by culture-dependent and independent methods. Culturable aerobic and facultative anaerobic bacterial diversity was studied in saliva collected from 267 postpartum and 54 nonpregnant females by using standard microbiological methods. For unculturable bacterial diversity, DNA from saliva samples of four selected females was sequenced by targeting V4 region of 16S rRNA. In postpartum females, S. mutans was significantly more prevalent. Its colonization was also seen significant among females having gingivitis (P < 0.01), dental caries (P < 0.01), and in those giving birth to low weight baby. In postpartum group, 65.16% females were culture positive for Staphylococcus, 12.73% Gram positive rods, 10.48% N. meningitides, 6.36% K. pneumoniae, 5.61% Enterobacter species and 2.62% E. coli. Isolates showed high biofilm forming ability and antibiotic resistance. Upon analysis of unculturable bacterial diversity, a total of 16 phyla and 156 genera were observed. Alpha diversity was decrease in postpartum female having oral health issues with pre-term low weight birth, compared to females with full term birth. Bray-Curtis dissimilarity was highest between female with dental issues and different pregnancy outcomes. Bacterial diversity and abundance altered among females with different oral health conditions and pregnancy outcomes, and also have pathogenic potential.

Imatinib-Resistant Gastrointestinal Stromal Tumor Presenting as a Large Abdominal Mass.

Gastrointestinal stromal tumors (GISTs) are the stromal or mesenchymal neoplasms affecting the gastrointestinal tract. Although they constitute 1% of primary gastrointestinal tumors, they are the most common nonepithelial tumors involving the gastrointestinal tract. They mostly present as overt or occult gastrointestinal bleeding. We present a case in which a 77-year-old female presented with a large abdominal mass. The origin of the mass was unclear on CT and MRI scan of the abdomen. Upper gastrointestinal endoscopic ultrasonography showed a cystic lesion in the perigastric region. A fine-needle biopsy of the lesion was performed, which was consistent with spindle type GIST. After the initial failure of imatinib therapy, the tumor was managed surgically.

May-Thurner Syndrome: A Rare Case of Unilateral Deep Vein Thrombosis in an Elderly Woman.

BACKGROUND Deep vein thrombosis (DVT) is a critical disorder with a high incidence and a high disease burden. Multiple acquired and genetic factors leading to hypercoagulation, venous injury, and venous stasis account for its basic pathophysiology. One of the rarely considered underlying etiologies of DVT is May-Thurner Syndrome (MTS), also known as iliac vein compression syndrome. MTS is an anatomical variant in which the left common iliac vein is extrinsically compressed by the right common iliac artery against the lumbar spine, leading to the development of iliofemoral DVT. CASE REPORT We present the case of a 78-year-old woman who presented with chronic unilateral lower-extremity swelling and pain. Ultrasound was consistent with extensive DVT extending from the left common femoral vein to left popliteal vein. Further workup revealed left common iliac venous outflow obstruction due to the extrinsic compression by the overlying atherosclerotic calcified right common iliac artery crossing against the lumbosacral region. CONCLUSIONS MTS usually presents in the second to fourth decades of life, making it challenging to consider it as a differential diagnosis in older patients. The conventional treatment of DVT with anticoagulation alone is insufficient to address thrombotic MTS and can lead to recurrent DVT, post-thrombotic syndrome, and life-threatening complications. Our patient presented in the seventh decade of life, warranting a high index of clinical suspicion of MTS in patients presenting with unilateral leg DVT, regardless of patient age, for timely diagnosis and appropriate therapeutic management.

Organ-Specific Hypereosinophilic Syndrome Presenting as Eosinophilic Gastroenteritis.

Gastrointestinal (GI) diseases have a substantial impact on the population health and healthcare resources of the United States. They constitute billions of dollars in expenditure and millions of office and hospital visits. With advancing diagnostic and treatment modalities, rare diseases are increasingly recognized and managed. However, after close to 80 years since the first description, eosinophilic GI disorders (EGID) are still uncommon, and only around 300 cases have been reported to date. Hypereosinophilic syndrome (HES) is well studied, but there are still no guidelines to direct management. We report the case of a 56-year-old female who presented with gastroenteritis and a persistent eosinophil count above 7 x 109/L. Imaging was suggestive of bowel wall thickening, and endoscopy revealed normal-appearing mucosa. However, histologic examination revealed eosinophilic infiltration of the GI tract. She was diagnosed with HES and treated with oral prednisone with remarkable improvement of her symptoms.

Biliary Sphincter of Oddi Dysfunction.

Sphincter of Oddi dysfunction (SOD) is a syndrome caused by either dyskinesia or stenosis of the sphincter of Oddi. It has been categorized into biliary and pancreatic SOD based on clinical features and laboratory findings. We present a case of a 51-year-old female (post-cholecystectomy) who presented with intermittent chronic right upper quadrant pain. Laboratory investigations showed persistently elevated liver function tests and a dilated common bile duct without the presence of any stones. Endoscopic retrograde cholangiopancreatography with manometry showed an elevated sphincter of Oddi pressure, thus confirming the diagnosis of SOD. She underwent endoscopic sphincterotomy and papillotomy with normalization of liver function tests and resolution of her chronic symptoms.

Erythrocytosis, embolism in a woman with antiphospholipid antibodies: A diagnostic challenge.

Systemic thromboembolism, along with acute multiorgan failure, should raise clinical suspicion for CAPS. Timely management, even in suspected cases, can have a significant impact on mortality.