Shape-Controlled First-Row Transition Metal Vanadates for Electrochemical and Photoelectrochemical Water Splitting.

Transition metal vanadates (MVs) possess abundant electroactive sites, short ion diffusion pathways, and optical properties that make them suitable for various electrochemical (EC) and photoelectrochemical (PEC) applications. While these materials are commonly used in energy storage devices like batteries and capacitors, their shape-controlled 1D and 2D morphologies have gained equal popularity in water splitting (WS) technology in recent times. This review focuses on recent progress made on various first-row (3d, 4 s) transition metal vanadates (t-MVs) having controlled one-dimensional (fiber, wire, or rod) and two-dimensional (layered or sheet) morphologies with a specific emphasis on copper vanadates (CuV), cobalt vanadates (CoV), iron vanadates (FeV), and nickel vanadates (NiV). The review covers different aspects of shape-controlled 1D and 2D t-MVs including optoelectrical properties, wet chemistry synthesis, and electrochemical (EC-WS) and photoelectrochemical water splitting (PEC-WS) performance in terms of onset potential, overpotential, and long-term stability or high cyclic performance. The review concludes by providing some possible thoughts on how to promote the water-splitting attributes of shape-controlled t-MVs more effectively.

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.

Exploring the potential of halotolerant bacteria from coastal regions to mitigate salinity stress in wheat: physiological, molecular, and biochemical insights.

Salinity stress, a significant global abiotic stress, is caused by various factors such as irrigation with saline water, fertilizer overuse, and drought conditions, resulting in reduced agricultural production and sustainability. In this study, we investigated the use of halotolerant bacteria from coastal regions characterized by high salinity as a solution to address the major environmental challenge of salinity stress. To identify effective microbial strains, we isolated and characterized 81 halophilic bacteria from various sources, such as plants, rhizosphere, algae, lichen, sea sediments, and sea water. We screened these bacterial strains for their plant growth-promoting activities, such as indole acetic acid (IAA), phosphate solubilization, and siderophore production. Similarly, the evaluation of bacterial isolates through bioassay revealed that approximately 22% of the endophytic isolates and 14% of rhizospheric isolates exhibited a favorable influence on seed germination and seedling growth. Among the tested isolates, GREB3, GRRB3, and SPSB2 displayed a significant improvement in all growth parameters compared to the control. As a result, these three isolates were utilized to evaluate their efficacy in alleviating the negative impacts of salt stress (150 mM, 300 mM, and seawater (SW)) on the growth of wheat plants. The result showed that shoot length significantly increased in plants inoculated with bacterial isolates up to 15% (GREB3), 16% (GRRB3), and 24% (SPSB2), respectively, compared to the control. The SPSB2 strain was particularly effective in promoting plant growth and alleviating salt stress. All the isolates exhibited a more promotory effect on root length than shoot length. Under salt stress conditions, the GRRB3 strain significantly impacted root length, leading to a boost of up to 6%, 5%, and 3.8% at 150 mM, 300 mM, and seawater stress levels, respectively. The bacterial isolates also positively impacted the plant's secondary metabolites and antioxidant enzymes. The study also identified the WDREB2 gene as highly upregulated under salt stress, whereas DREB6 was downregulated. These findings demonstrate the potential of beneficial microbes as a sustainable approach to mitigate salinity stress in agriculture.

Bandgap Engineering of Melon using Highly Reduced Graphene Oxide for Enhanced Photoelectrochemical Hydrogen Evolution.

The uncondensed form of polymeric carbon nitrides (PCN), generally known as melon, is a stacked 2D structure of poly(aminoimino)heptazine. Melon is used as a photocatalyst in solar energy conversion applications, but suffers from poor photoconversion efficiency due to weak optical absorption in the visible spectrum, high activation energy, and inefficient separation of photoexcited charge carriers. Experimental and theoretical studies are reported to engineer the bandgap of melon with highly reduced graphene oxide (HRG). Three HRG@melon nanocomposites with different HRG:melon ratios (0.5%, 1%, and 2%) are prepared. The 1% HRG@melon nanocomposite shows higher photocurrent density (71 µA cm-2 ) than melon (24 µA cm-2 ) in alkaline conditions. The addition of a hole scavenger further increases the photocurrent density to 630 µA cm-2 relative to the reversible hydrogen electrode (RHE). These experimental results are validated by calculations using density functional theory (DFT), which revealed that HRG results in a significant charge redistribution and an improved photocatalytic hydrogen evolution reaction (HER).

Enhanced Physiological and Biochemical Performance of Mung Bean and Maize under Saline and Heavy Metal Stress through Application of Endophytic Fungal Strain SL3 and Exogenous IAA.

Modern irrigation practices and industrial pollution can contribute to the simultaneous occurrence of salinity and heavy metal contamination in large areas of the world, resulting in significant negative effects on crop productivity and sustainability. This study aimed to investigate the growth-promoting potentials of an important endophytic fungal strain SL3 and to compare its potential with exogenous IAA (indole-3-acetic acid) in the context of salt and heavy metal stress. The strain was assessed for plant growth-promoting traits such as the production of indole-3-acetic acid, gibberellins (GA), and siderophore. We selected two important crops, mung bean and maize, and examined various physiological and biochemical characteristics under 300 mM NaCl and 2.5 mM Pb stress conditions, with and without the application of IAA and SL3. This study's results demonstrated that both IAA and SL3 positively impacted the growth and development of plants under normal and stressed conditions. In NaCl and Pb-induced stress conditions, the growth of mung bean and maize plants was significantly reduced. However, the application of IAA and SL3 helped to alleviate stress, leading to a significant increase in shoot/root length and weight compared to IAA and SL3 non-treated plants. The results revealed that photosynthetic pigments, accumulation of catalase (CAT), phenolic contents, polyphenol oxidase, and flavanols are higher in the IAA and SL3-treated plants than in the non-inoculated plants. This study's findings revealed that applying the SL3 fungal strain positively influenced various physiological and biochemical processes in tested plant species under normal and stress conditions of NaCl and Pb. These findings also suggested that SL3 could be a potential replacement for widely used IAA to promote plant growth by improving photosynthetic efficiency, reducing oxidative stress, and enhancing metabolic activities in plants, including mung and maize. Moreover, this study highlights that SL3 has synergistic effects with IAA in enhancing resilience to salt and heavy stress and offers a promising avenue for future agricultural applications in salt and heavy metal-affected regions.

Efficient photodegradation of methyl red dye by kaolin clay supported zinc oxide nanoparticles with their antibacterial and antioxidant activities.

Kaolin clay-supported Zinc oxide (ZnO/KC) and ZnO NPs nanoparticles (NPs) were prepared by a chemical reduction process and used for the photodegradation of methyl red (MR) dye as a photocatalyst. Due to the interlayered porous structure of the KC, we achieved an extremely good association between ZnO NPs and KC. The product confirmation was conducted by Scanning electron microscopy (SEM), X-Ray diffraction (XRD), energy dispersive X-Ray (EDX), and Fourier transforms infrared (FTIR). SEM showed the irregular morphology of ZnO NPs, while ZnO/KC NCs were predominately round-shaped. Moreover, in both cases, NPs were present in both dispersed as well as agglomerated forms with an average particle size below 100 nm. The results acquired from photodegradation analyses show that ZnO NPs and ZnO/KC NCs degraded about 90 and 99% of MR dye respectively, under UV light in a short irradiation time of 10 min. The recovered and re-recovered ZnO NPs and ZnO/KC NCs also considerably photodegraded MR dye in an aqueous medium. The same NPs also exhibit promising bioactivities against two pathogenic bacteria, i.e., Citrobacter and Providencia. The antioxidant activity of ZnO/KC NCs reached to reasonable 70% compared to the 88% activity of the standard ascorbic acid.

Dynamic interplay of WRKY, GRAS, and ERF transcription factor families in tomato-endophytic fungal symbiosis: insights from transcriptome and genome-wide analysis.

Plant-microbe interactions play a crucial role in shaping plant growth and development, as well as in mediating plant responses to biotic and abiotic stresses. In this study, we used RNA-seq data to examine the expression profiles of SlWRKY, SlGRAS, and SlERF genes during the symbiotic association of Curvularia lunata SL1 with tomato (Solanum lycopersicum) plants. We also conducted functional annotation analysis by comparative genomics studies of their paralogs and orthologs genes, as well as other approaches, such as gene analysis and protein interaction networks, to identify and characterize the regulatory roles of these TFs in the development of the symbiotic association. We found that more than half of the investigated SlWRKY genes exhibited significant upregulation during symbiotic association, including SlWRKY38, SlWRKY46, SlWRKY19, and SlWRKY51. Several SlGRAS and SlERF genes were upregulated, such as SlGLD2, SlGLD1, SlERF.C.5, ERF16, and SlERF.B12. Conversely, a smaller proportion of SlWRKY, SlGRAS, and SlERF genes were significantly downregulated during symbiotic association. Furthermore, we investigated the possible roles of SlWRKY, SlGRAS, and SlERF genes in hormonal regulation during plant-microbe interactions. We identified several upregulated candidate transcripts likely to be involved in plant hormone signaling pathways. Our findings are consistent with previous studies on these genes, providing further evidence of their involvement in hormonal regulation during plant-microbe interactions. To validate the RNA-seq data accuracy, we performed RT-qPCR analyses of selected SlWRKY, SlGRAS, and SlERF genes, which showed similar expression patterns to those observed in the RNA-seq data. These results confirmed the accuracy of our RNA-seq data and provided additional support for the differential expression of these genes during plant-microbe interactions. Taken together, our study provides new insights into the differential expression profiles of SlWRKY, SlGRAS, and SlERF genes during symbiotic association with C. lunata, as well as their potential roles in hormonal regulation during plant-microbe interactions. These findings could be useful for guiding future research on the ways in which plants and microbes interact, and may ultimately lead to the creation of better approaches for promoting plant growth under stressful conditions.

Photoreforming of Waste Polymers for Sustainable Hydrogen Fuel and Chemicals Feedstock: Waste to Energy.

Energy from renewable resources is central to environmental sustainability. Among the renewables, sunlight-driven fuel synthesis is a sustainable and economical approach to produce vectors such as hydrogen through water splitting. The photocatalytic water splitting is limited by the water oxidation half-reaction, which is kinetically and energetically demanding and entails designer photocatalysts. Such challenges can be addressed by employing alternative oxidation half-reactions. Photoreforming can drive the breakdown of waste plastics and biomass into valuable organic products for the production of H2. We provide an overview of photoreforming and its underlying mechanisms that convert waste polymers into H2 fuels and fine chemicals. This is of paramount importance from two complementary perspectives: (i) green energy harvesting and (ii) environmental sustainability by decomposing waste polymers into valuables. Competitive results for the generation of H2 fuel without environmental hazards through photoreforming are being generated. The photoreforming process, mechanisms, and critical assessment of the field are scarce. We address such points by focusing on (i) the concept of photoreforming and up-to-date knowledge with key milestones achieved, (ii) uncovering the concepts and challenges in photoreforming, and (iii) the design of photocatalysts with underlying mechanisms and pathways through the use of different polymer wastes as substrates.

Polypill Therapy in Cardiovascular Disease: A Meta-Analysis of Randomized Controlled Trials.

The effectiveness of polypill therapy in the prevention and treatment of cardiovascular disorders is still unclear. This meta-analysis aimed to assess the efficacy of polypill therapy in reducing cardiovascular risk factors. We conducted a systematic search of PubMed, Cochrane CENTRAL, SCOPUS, and Google Scholar for randomized controlled trials (RCTs) that evaluated polypill therapy for cardiovascular diseases, hypertension, or dyslipidemia. We included 18 RCTs with a total of 20,463 participants in our analysis. Pooled effect estimates were reported as Odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Polypill therapy was associated with a statistically significant reduction in systolic blood pressure (SBP) (OR: -0.33, 95% CI [-0.64, -0.03]; P-value = 0.03), diastolic blood pressure (DBP) (OR: -0.70, 95% CI [-1.20, -0.21]; P-value = 0.005), and total cholesterol level (OR: -1.25, 95% CI [-1.82, -0.68]; P-value < 0.0001). Polypill therapy also showed improved adherence (OR 2.18, 95% CI [1.47, 3.24]; P-value = 0.0001). However, there was no statistically significant benefit in the reduction of all-cause mortality, major cardiovascular events, and LDL-c levels. The use of polypill therapy is associated with a statistically significant reduction in SBP, DBP, and total cholesterol levels, as well as improved adherence. Further research is needed to determine its impact on hard clinical outcomes such as mortality and major cardiovascular events.

Characterization of the Seed Biopriming, Plant Growth-Promoting and Salinity-Ameliorating Potential of Halophilic Fungi Isolated from Hypersaline Habitats.

Salinity stress is one of the major abiotic factors limiting crop yield in arid and semi-arid regions. Plant growth-promoting fungi can help plants thrive in stressful conditions. In this study, we isolated and characterized 26 halophilic fungi (endophytic, rhizospheric, and soil) from the coastal region of Muscat, Oman, for plant growth-promoting activities. About 16 out of 26 fungi were found to produce IAA, and about 11 isolates (MGRF1, MGRF2, GREF1, GREF2, TQRF4, TQRF5, TQRF5, TQRF6, TQRF7, TQRF8, TQRF2) out of 26 strains were found to significantly improve seed germination and seedling growth of wheat. To evaluate the effect of the above-selected strains on salt tolerance in wheat, we grew wheat seedlings in 150 mM, 300 mM NaCl and SW (100% seawater) treatments and inoculated them with the above strains. Our findings showed that fungal strains MGRF1, MGRF2, GREF2, and TQRF9 alleviate 150 mM salt stress and increase shoot length compared to their respective control plants. However, in 300 mM stressed plants, GREF1 and TQRF9 were observed to improve shoot length. Two strains, GREF2 and TQRF8, also promoted plant growth and reduced salt stress in SW-treated plants. Like shoot length, an analogous pattern was observed in root length, and different salt stressors such as 150 mM, 300 mM, and SW reduced root length by up to 4%, 7.5%, and 19.5%, respectively. Three strains, GREF1, TQRF7, and MGRF1, had higher catalase (CAT) levels, and similar results were observed in polyphenol oxidase (PPO), and GREF1 inoculation dramatically raised the PPO level in 150 mM salt stress. The fungal strains had varying effects, with some, such as GREF1, GREF2, and TQRF9, showing a significant increase in protein content as compared to their respective control plants. Under salinity stress, the expression of DREB2 and DREB6 genes was reduced. However, the WDREB2 gene, on the other hand, was shown to be highly elevated during salt stress conditions, whereas the opposite was observed in inoculated plants.

The Assessment of Antimicrobial Resistance in Gram-Negative and Gram-Positive Infective Endocarditis: A Multicentric Retrospective Analysis.

Background and Objectives: Multidrug-resistant microorganisms have made treating bacterial infections challenging. Resistance to antibiotics is expected to overcome efforts to produce new, effective antibacterial medication that is lifesaving in many situations. Infective endocarditis (IE) is a life-threatening infection that affects 5-15 per 100,000 patients annually and requires rapid antibiotic therapy to prevent morbidity and mortality. Materials and Methods: The present research assessed IE cases over five years, from a multicentric database, with the main objective of determining the degree of antibiotic resistance in these patients, stratified by Gram-positive and Gram-negative bacteria. Results: Bad oral hygiene was present in 58.6% of patients from the Gram-negative group (vs. 38.7% in the Gram-positive group). Non-valvular heart disease was identified in approximately 40% of all patients, and valvopathies in approximately 20%. It was observed that 37.9% of Gram-negative IE bacteria were resistant to three or more antibiotics, whereas 20.7% were susceptible. Among Gram-positive infections, S. aureus was the most commonly involved pathogen, with a multidrug-resistant pattern in 11.2% of patients, while Acinetobacter baumannii had the highest resistance pattern of all Gram-negative pathogens, with 27.4% of all samples resistant to three or more antibiotics. Patients with Gram-negative IE were 4.2 times more likely to die. The mortality risk was 4 times higher when bacteria resistant to two or more antibiotics was involved and 5.7 times higher with resistance patterns to three or more antibiotics than the reference group with no antibiotic resistance. Peripheral catheters were the most common cause of multi-resistant IE, followed by heart surgery, dental procedures, and ENT interventions. Conclusions: Even though Gram-positive infections were the most frequent (83.0% of all cases), Gram-negative IE infections are substantially more deadly than Gram-positive IE infections. However, it was also observed that patients with Gram-negative infections were more likely to have underlying comorbidities, be institutionalized, and be underweight. Although the Gram-negative infections were more severe, their resistance patterns were similar to Gram-positive bacteria. As resistance patterns increase, more efforts should be made to prevent a healthcare catastrophe. At the same time, careful prophylaxis should be considered in patients at risk, including those with central catheters, undergoing dental procedures, and with poor oral hygiene.

Pathological Complete Response of Metastatic Clear Cell Renal Carcinoma with Pembrolizumab and Axitinib: A Case Report and Review of Literature.

The role of cytoreductive nephrectomy has become unclear since the introduction of immunotherapy which is now the backbone of the treatment for metastatic renal cell carcinoma. Different combinations are used based on the prognosis. Achieving a complete response would be ideal and includes radiographic disappearance of lesions. However, there have been a few reported cases of pathological complete response with persistent radiographic evidence of cancer. The authors report a case of pathological complete response despite persistent radiographic evidence of residual disease in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib. The patient subsequently underwent cytoreductive nephrectomy after the 13th dose of pembrolizumab. The resected mass consisted of scar tissue with no viable tumor cells seen on pathology but only scar tissue. This case reveals that persistent radiographic evidence of the tumor may be explained by scar tissue, challenging the role of cytoreductive nephrectomy in the era of immunotherapy.

Genome-wide annotation and expression analysis of WRKY and bHLH transcriptional factor families reveal their involvement under cadmium stress in tomato (Solanum lycopersicum L.).

The WRKY and bHLH transcription factors have been implicated in the regulation of gene expression during various physiological processes in plants, especially in plant stress responses. However, little information about the heavy metal-responsive SlWRKY and SlbHLH in tomato (Solanum lycopersicum) is available. We performed a genome-wide investigation for these two TF families in S. lycopersicum and determined their role in cadmium (Cd) stress tolerance. Furthermore, ortholog analysis with the Arabidopsis genome led to classifying WRKY and bHLH ortholog genes into nine and 11 clusters, respectively. The comparative phylogenetic analysis revealed duplication events and gene loss in Arabidopsis and S. lycopersicum, which occurred during evolution both before and after the last common ancestor of the two species. Orthologous relationships are also supported by additional evidence, such as gene structure, conserved motif compositions, and protein-protein interaction networks for the majority of genes, suggesting their similar functions. A comprehensive transcriptomics analysis revealed that both WRKY and bHLH genes were differentially expressed in response to cadmium stress as compared with control plants. A gene ontology analysis revealed that most WRKYs and bHLHs are DNA-binding essential proteins that regulate gene expression positively and negatively. Analyses of interaction networks revealed that both WRKYs and bHLHs mediate networks implicated in several stress-signaling pathways. The findings of this work may help us to comprehend the intricate transcriptional control of WRKY and bHLH genes and identify potential stress-responsive genes relevant to tomato genetic improvement. Moreover, identifying heavy metal stress-responsive WRKY and bHLH genes in S. lycopersicum will provide fundamental insights for developing new heavy metal stress-tolerant varieties of tomato crops.

Diversity, Lifestyle, Genomics, and Their Functional Role of Cochliobolus, Bipolaris, and Curvularia Species in Environmental Remediation and Plant Growth Promotion under Biotic and Abiotic Stressors.

Cochliobolus, Bipolaris, and Curvularia genera contain various devastating plant pathogens that cause severe crop losses worldwide. The species belonging to these genera also perform a variety of diverse functions, including the remediation of environmental contaminations, beneficial phytohormone production, and maintaining their lifestyle as epiphytes, endophytes, and saprophytes. Recent research has revealed that despite their pathogenic nature, these fungi also play an intriguing role in agriculture. They act as phosphate solubilizers and produce phytohormones, such as indole acetic acid (IAA) and gibberellic acid (GAs), to accelerate the growth of various plants. Some species have also been reported to play a significant role in plant growth promotion during abiotic stresses, such as salinity stress, drought stress, heat stress, and heavy metal stress, as well as act as a biocontrol agent and a potential mycoherbicide. Similarly, these species have been reported in numerous industrial applications to produce different types of secondary metabolites and biotechnological products and possess a variety of biological properties, such as antibacterial, antileishmanial, cytotoxic, phytotoxic, and antioxidant activities. Additionally, some of the species have been utilized in the production of numerous valuable industrial enzymes and biotransformation, which has an impact on the growth of crops all over the world. However, the current literature is dispersed, and some of the key areas, such as taxonomy, phylogeny, genome sequencing, phytohormonal analysis, and diversity, are still being neglected in terms of the elucidation of its mechanisms, plant growth promotion, stress tolerance, and bioremediation. In this review, we highlighted the potential role, function, and diversity of Cochliobolus, Curvularia, and Bipolaris for improved utilization during environmental biotechnology.

Genome and Transcriptome-Wide Analysis of OsWRKY and OsNAC Gene Families in Oryza sativa and Their Response to White-Backed Planthopper Infestation.

Plants are threatened by a wide variety of herbivorous insect assaults, and display a variety of inherent and induced defenses that shield them against herbivore attacks. Looking at the massive damage caused by the white-backed planthopper (WBPH), Sogatella furcifera, we undertook a study to identify and functionally annotate OsWRKY and OsNAC transcription factors (TFs) in rice, especially their involvement in WBPH stress. OsWRKY and OsNAC TFs are involved in various developmental processes and responses to biotic and abiotic stresses. However, no comprehensive reports are available on the specific phycological functions of most of the OsWRKY and OsNAC genes in rice during WBPH infestation. The current study aimed to comprehensively explore the OsWRKY and OsNAC genes by analyzing their phylogenetic relationships, subcellular localizations, exon-intron arrangements, conserved motif identities, chromosomal allocations, interaction networks and differential gene expressions during stress conditions. Comparative phylogenetic trees of 101 OsWRKY with 72 AtWRKY genes, and 121 OsNAC with 110 AtNAC genes were constructed to study relationships among these TFs across species. Phylogenetic relationships classified OsWRKY and OsNAC into eight and nine clades, respectively. Most TFs in the same clade had similar genomic features that represented similar functions, and had a high degree of co-expression. Some OsWRKYs (Os09g0417800 (OsWRKY62), Os11g0117600 (OsWRKY50), Os11g0117400 (OsWRKY104) and OsNACs (Os05g0442700, Os12g0630800, Os01g0862800 and Os12g0156100)) showed significantly higher expressions under WBPH infestation, based on transcriptome datasets. This study provides valuable information and clues about predicting the potential roles of OsWRKYs and OsNACs in rice, by combining their genome-wide characterization, expression profiling, protein-protein interactions and gene expressions under WBPH stress. These findings may require additional investigation to understand their metabolic and expression processes, and to develop rice cultivars that are resistant to WBPH.

Stage 4 Cytokine Release Syndrome Caused by the First Dose of Nivolumab and Ipilimumab Combination Therapy in a Patient with Metastatic Melanoma Successfully Treated with Methylprednisolone, Tocilizumab, and Etanercept.

The authors report the first case of stage 4 cytokine release syndrome (CRS) (graded by the National Cancer Institute Common Terminology Criteria for Adverse Effects scale) involving a patient with advanced metastatic melanoma who was treated with the combination of two monoclonal antibodies, nivolumab (anti-programmed cell death receptor 1 inhibitor [PD-1]) and ipilimumab (a cytotoxic T lymphocyte-associated antigen 4 inhibitor [CTLA-4]) after her first dose of both. The patient was treated initially with methylprednisolone and tocilizumab but was refractory to treatment. A trial of etanercept was initiated due to her elevated levels of TNF-α which elicited a satisfactory response. Monoclonal antibody therapy is a new tool for the treatment of many cancers, and therefore there may be a subsequent rise in the cases of CRS and this case exemplifies a treatment algorithm. Utilizing levels of cytokines assists in tailoring treatment such as in this case where etanercept, a TNF-α inhibitor, was utilized due to the patient's elevated levels of TNF-α.

Unilateral Erosive Arthritis Following Moderna COVID-19 Vaccination.

A novel coronavirus was identified at the end of 2019, causing a pneumonia epidemic in China, which later rapidly spread to cause a global pandemic. However, most people who contracted the COVID-19 had mild to moderate symptoms. A fair percentage developed ARDS, Septic shock, and multi-organ failure. Given the necessity of immunization in combating this disease, COVID-19 vaccines were widely deployed, giving rise to multiple reported cases of post-vaccination autoimmune flareups and new onset of autoimmune phenomena. We present a case of an 81-year-old female who was diagnosed with erosive arthritis post COVID-19 vaccination.

Lupeol Treatment Attenuates Activation of Glial Cells and Oxidative-Stress-Mediated Neuropathology in Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) signifies a major cause of death and disability. TBI causes central nervous system (CNS) damage under a variety of mechanisms, including protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Astrocytes and microglia, cells of the CNS, are considered the key players in initiating an inflammatory response after injury. Several evidence suggests that activation of astrocytes/microglia and ROS/LPO have the potential to cause more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that lupeol provides neuroprotection through modulation of inflammation, oxidative stress, and apoptosis in Aß and LPS model and neurodegenerative disease. However, the effects of lupeol on apoptosis caused by inflammation and oxidative stress in TBI have not yet been investigated. Therefore, we explored the role of Lupeol on antiapoptosis, anti-inflammatory, and antioxidative stress and its potential mechanism following TBI. In these experiments, adult male mice were randomly divided into four groups: control, TBI, TBI+ Lupeol, and Sham group. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of lupeol against neuroinflammation, oxidative stress, and apoptosis. Lupeol treatment reversed TBI-induced behavioral and memory disturbances. Lupeol attenuated TBI-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1) in the mouse brain. Similarly, our results indicated that lupeol treatment inhibited glial cell activation, p-NF-κB, and downstream signaling molecules, such as TNF-α, COX-2, and IL-1ß, in the mouse cortex and hippocampus. Moreover, lupeol treatment also inhibited mitochondrial apoptotic signaling molecules, such as caspase-3, Bax, cytochrome-C, and reversed deregulated Bcl2 in TBI-treated mice. Overall, our study demonstrated that lupeol inhibits the activation of astrocytes/microglia and ROS/LPO that lead to oxidative stress, neuroinflammation, and apoptosis followed by TBI.

Spontaneous Tumor Lysis Syndrome in a Patient with Bulky Chronic Lymphocytic Leukemia Diagnosed after Resolution of Symptoms.

Tumor lysis syndrome (TLS) is an oncologic emergency characterized by the destruction of tumor cells leading to an influx of large amounts of uric acid, potassium, and phosphorus into systemic circulation. It most often occurs after the initiation of cytotoxic therapy in high-grade lymphomas and leukemias; however, rarely it may occur spontaneously. The authors report a case of spontaneous tumor lysis causing electrolyte abnormalities and acute kidney injury in a patient with subsequently diagnosed large chronic lymphocytic leukemia tumor burden. Spontaneous TLS can be the first presentation of underlying malignancy; therefore, physicians should be aware of the associated findings.

Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection.

K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflammatory myeloid cells. In this setting, metabolically active Kp ST258 elicits a disease-tolerant immune response. The bacteria, in turn, adapt to airway oxidants by upregulating the type VI secretion system, which is highly conserved across ST258 strains worldwide. Thus, much of the global success of Kp ST258 in hospital settings can be explained by the metabolic activity provoked in the host that promotes disease tolerance.