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The European physical journal / C 81(11), 992 (2021). doi:10.1140/epjc/s10052-021-09712-6, We assess the status of a wide class of WIMP dark matter (DM) models in light of the latest experimental results using the global fitting framework GAMBIT. We perform a global analysis of effective field theory (EFT) operators describing the interactions between a gauge-singlet Dirac fermion and the Standard Model quarks, the gluons and the photon. In this bottom-up approach, we simultaneously vary the coefficients of 14 such operators up to dimension 7, along with the DM mass, the scale of new physics and several nuisance parameters. Our likelihood functions include the latest data from Planck, direct and indirect detection experiments, and the LHC. For DM masses below 100 GeV, we find that it is impossible to satisfy all constraints simultaneously while maintaining EFT validity at LHC energies. For new physics scales around 1 TeV, our results are influenced by several small excesses in the LHC data and depend on the prescription that we adopt to ensure EFT validity. Furthermore, we find large regions of viable parameter space where the EFT is valid and the relic density can be reproduced, implying that WIMPs can still account for the DM of the universe while being consistent with the latest data., Published by Springer, Heidelberg

Coronavirus disease 2019 (COVID-19) is the third deadly coronavirus infection of the 21st century that has proven to be significantly more lethal than its predecessors, with the number of infected patients and deaths still increasing daily. From December 2019 to July 2021, this virus has infected nearly 200 million people and led to more than 4 million deaths. Our understanding of COVID-19 is constantly progressing, giving better insight into the heterogeneous nature of its acute and long-term effects. Recent literature on the long-term health consequences of COVID-19 discusses the need for a comprehensive understanding of the multisystemic pathophysiology, clinical predictors, and epidemiology to develop and inform an evidence-based, multidisciplinary management approach. A PubMed search was completed using variations on the term post-acute COVID-19. Only peer-reviewed studies in English published by July 17, 2021 were considered for inclusion. All studies discussed in this text are from adult populations unless specified (as with multisystem inflammatory syndrome in children). The preliminary evidence on the pulmonary, cardiovascular, neurological, hematological, multisystem inflammatory, renal, endocrine, gastrointestinal, and integumentary sequelae show that COVID-19 continues after acute infection. Interdisciplinary monitoring with holistic management that considers nutrition, physical therapy, psychological management, meditation, and mindfulness in addition to medication will allow for the early detection of post-acute COVID-19 sequelae symptoms and prevent long-term systemic damage. This review serves as a guideline for effective management based on current evidence, but clinicians should modify recommendations to reflect each patient's unique needs and the most up-to-date evidence. The presence of long-term effects presents another reason for vaccination against COVID-19.

Targeted covalent inhibitors are powerful entities in drug discovery, but their application has so far mainly been limited to addressing cysteine residues. The development of cysteine-directed covalent inhibitors has largely profited from determining their proteome-wide selectivity using competitive residue-specific proteomics. Several probes have recently been described to monitor other amino acids using this technology and many more electrophiles exist to modify proteins. Nevertheless, a direct, proteome‑wide comparison of the selectivity of diverse probes is still entirely missing. Here, we developed a completely unbiased workflow to analyse electrophile selectivity proteome‑wide and applied it to directly compare 54 alkyne probes containing diverse reactive groups. In this way, we verified and newly identified probes to monitor a total of nine different amino acids as well as the N‑terminus proteome‑wide. This selection includes the first probes to globally monitor tryptophans, histidines and arginines as well as novel tailored probes for methionines, aspartates and glutamates.

Smoke produced by traditional open surgery (TOS) has long been considered hazardous to medical staff. Compared with TOS, minimally invasive surgery under carbon dioxide pneumoperitoneum is associated with a faster recovery and less wound pain. However, the impact of oxygen-deficient environment on the chemical contents of smoke has not been comprehensively assessed.This research evaluated the chemical composition and volatile organic compound (TVOC) level in smoke produced by open cholecystectomy (OC) versus laparoscopic cholecystectomy (LC) for gallbladder diseases. Smoke samples were collected and analyzed via gas chromatography-mass spectrometry. Chemical compounds were further grouped according to molecular weight and toxicity.Compared with the OC, LC had significantly higher halocarbon and TVOC levels but lower cycloalkene and aldehyde levels. No halocarbons were isolated from OC specimens. When stratified based on molecular weight, LC had a bimodal pattern (i.e., high levels of small-sized [60 Da] and large-sized [120 Da] compounds). There was no difference in terms of toxicity types, incidence, and severity associated with detected compounds between two groups.LC is associated with a higher TVOC level and proportion of low- and high-molecular-weight organic compounds. Further strategies of evacuating these health hazards and preventing smoke leakage through trocars should be considered.

Background: Hymenoptera stings are one of the common causes of anaphylaxis. The prevalence of systemic allergic reactions seems to be higher in highly exposed populations such as beekeepers and individuals receiving live bee acupuncture (LBA). However, there are a very few of studies on venom allergy in these populations. We performed two observational studies to describe the characteristics and risk factors of venom allergy in beekeepers and the LBA population.Methods: A total of 99 beekeepers and 127 individuals receiving live bee acupuncture were interviewed. Skin prick tests were performed on subjects with suspected bee venom allergy.Results: The prevalence of bee venom allergy was 34.3% among beekeepers and 29.0% in the LBA population. Systemic reactions occurred in 11.3% of the LBA population, and 28.3% of beekeepers. For beekeepers with exposure to 2-4 stings per year and ≥5 stings per year, the risk for developing venom allergy increased to 6.745-fold (95% CI 2.139-21.266) and 42.297-fold (95% CI 7.060-253.399) respectively, compared to the ≤1 sting per year group. Conversely, in the LBA population, compared to frequency ≤2 LBA stings per week, the adjusted OR of venom allergy was 0.281 (95% CI 0.075-1.047) and 0.166 (95% CI 0.045-0.612) for frequency 3-6 LBA stings per week and ≥7 stings per week respectively. The knowledge of adrenaline and venom immunotherapy was limited in both beekeepers and traditional doctors.Conclusion: The frequency of stings with high risk for bee venom allergy was >4/year in beekeepers and

Complex regional pain syndrome (CRPS) has been considered to be an autoimmune disease and there have been clinical trials with intravenous immunoglobulin. Often the etiology of the so-called CRPS diagnosis cannot be discerned and there are no validated instruments that provide functional metrics. The term complex regional pain syndrome (CRPS), coined in 1994 to describe patients in whom the pain is out of proportion to the injury, was actually a diagnosis proposed during the American Civil War, but was originally known as causalgia. Physicians have long observed similar sensitivity and inflammatory symptoms following periods of immobilization and disuse, which generally resolve within a few months of remobilization. Following the original description, persistent disproportionate pain would come to be known under many other names until researchers theorized that it was related to dysfunction in the sympathetic nervous system, after which it acquired the moniker, Reflex Sympathetic Dystrophy ("RSD"). In the latter quarter of the twentieth century, after researchers failed to prove the connection between the pain and the sympathetic nervous system, a small cadre of physicians-without rigorous science-invented CRPS. This new descriptor, CRPS, has become not only a diagnosis without objective data but with proposed criteria involving ambiguous signs and symptoms with low specificity. It has led to patients being treated erroneously with sympatholytic drugs, with or without pharmaceutical or surgical blockade of the sympathetic nervous system, unwarranted use of ketamine infusions, inappropriate use of narcotics and nerve stimulation. Intravenous immunoglobulin infusions have not been effective in the treatment of chronic pain. The indiscriminate use of pain medications to treat subjective symptoms of unclear diagnoses can be a risk factor for opioid and analgesic misuse or abuse.

Multiple myeloma continues to be a challenging disorder to treat despite improved therapies and the widespread use of proteasome inhibitors and immunomodulatory drugs. Although patient outcomes have improved, the disease continues to invariably relapse, and in the majority of cases, a cure remains elusive. In the last decade, there has been an explosion of novel drugs targeting cellular proteins essential for malignant plasma cell proliferation and survival. In this review, we focus on novel druggable targets leading to the development of monoclonal antibodies and cellular therapies against surface antigens (CD38, CD47, CD138, BCMA, SLAMF7, GPRC5D, FcRH5), inhibitors of epigenetic regulators such as histone deacetylase (HDAC), and agents targeting anti-apoptotic (BCL-2), ribosomal (eEF1A2) and nuclear export (XPO1) proteins.

We report a supramolecular porous organic cage platform composed of cobalt porphyrins for catalyzing the electrochemical hydrogen evolution reaction (HER) from water at neutral pH. Owing to its permanent porosity, the supramolecular structure yields a catalyst film with a 5-fold increase in the number of electrochemically active cobalt atoms and an improvement in Tafel slope from 170 mV/decade to 119 mV/decade compared to a planar cobalt porphyrin analog, reaching activities over 19,000 turnovers for HER over a 24-hour period with 100% Faradaic efficiency.

Lupus erythematosus (LE) is an autoimmune disease that is characterized by pathogenic autoantibodies and immunological attack of multiple organ systems, including the skin. The pathogenesis of skin damage in LE involves both genetic and epigenetic mechanisms. Various environmental triggers can induce LE. Exposure to ultraviolet radiation (UVR) is a prominent trigger factor. UVR has been shown to induce keratinocyte apoptosis and therefore give rise to the externalization of autoantigens, resulting in autoimmune response in skin. Possible downstream mechanisms include stimulation of an immune response through the activation and recruitment of dendritic cells and effector T cells. Certain cytokines and chemokines are upregulated in the process, including type 1 interferon and tumor necrosis factor alpha. In this chapter, we focus on the clinical aspects associated with skin damage and illustrate the underlying cellular and cytokine networks that result in skin damage in LE.

Background: Primary hypothyroidism due to autoimmune thyroiditis is extremely rare in infants, especially under the age of 3 years. For infants, hypothyroidism is most commonly congenital, originating from thyroid dysgenesis with an absent, ectopic, or hypoplastic thyroid gland (1 in 4,000 live births). If left untreated, it can lead to permanent neurodevelopmental deficits. In this report, we describe a male infant who was diagnosed with Hashimoto thyroiditis at 18 months of life, providing a learning example to aid in recognition of this rare disease and enable timely intervention. Clinical Case:Patient was a 2,765 gram, appropriate for gestational age, male born at term with hypospadias of the penis (surgical correction at 11 months). Patient passed meconium in the first 24 hours of life. During the first few months of life, patient developed constipation. Patient had amblyopia necessitating eye patching and began to wear eye glasses at 18 months of life. Patient’s linear and weight growth were within normal limits. Patient had normal motor development, however had language development delay. No known family history of thyroid disease. Screening labs performed at 17-months of age showed abnormal thyroid function: elevated TSH at 14.86 µIU/mL (ref: 0.45 - 4.50 µIU/mL) and normal free T4 level at 1.24 ng/dL (ref: 0.85-1.75 ng/dL). Repeat testing at 18 months of age continued to show elevated TSH at 6.18 µIU/mL (ref: 0.64 - 4.00 µIU/mL), normal free T4 at 1.07 ng/dL (ref: 0.88 - 2.03 ng/dL), and elevated thyroid peroxidase (TPO) antibodies at 163 IU/ml (ref: Conclusions: This case report provides insights into autoimmune thyroiditis in infancy, which, although especially rare under age 3 years, should be considered in infants who present with autoimmunity or abnormal thyroid testing. In the neonatal period, infants’ immune systems are learning to discriminate requirements for self-tolerance versus protection against pathogens and may be more prone to infections. Although autoimmunity in this stage of development is uncommon, there can be breakthroughs in tolerance, as seen in this case. In addition to this patient, two other infants were seen with elevated TPO antibodies, diagnosed at 17 and 31 months old, with similar clinical trends. There remains a need for additional studies providing further insights into autoimmunity in infancy. Importantly, this case illustrates that, when infants have abnormal thyroid levels (with or without other autoimmune conditions), consideration should be made for anti-thyroid antibody testing.

To facilitate computational investigation of intermolecular interactions in the solution phase, we report the development of ALMO-EDA(solv), a scheme that allows the application of continuum solvent models within the framework of energy decomposition analysis (EDA) based on absolutely localized molecular orbitals (ALMOs). In this scheme, all the quantum mechanical states involved in the variational EDA procedure are computed with the presence of solvent environment so that solvation effects are incorporated in the evaluation of all its energy components. After validation on several model complexes, we employ ALMO-EDA(solv) to investigate substituent effects on two classes of complexes that are related to electrochemical CO2 reduction catalysis. For [FeTPP(CO2−κC)]2− (TPP = tetraphenylporphyrin), we reveal that two ortho substituents which yield most favorable CO2 binding, −N(CH3)3+ (TMA) and −OH, stabilize the complex via through-structure and through-space mechanisms, respectively. The Coulombic interaction between the positively charged TMA group and activated CO2 is found to be largely attenuated by the polar solvent. Furthermore, we also provide computational support for the design strategy of utilizing bulky, flexible ligands to stabilize activated CO2 via long-range Coulomb interactions, which creates biomimetic solvent-inaccessible “pockets” in that electrostatics is unscreened. For the reactant and product complexes associated with the electron transfer from the p-terphenyl radical anion to CO2 , we demonstrate that the double terminal substitution of p-terphenyl by electron-withdrawing groups considerably strengthens the binding in the product state while moderately weakens that in the reactant state, which are both dominated by the substituent tuning of the electrostatics component. These applications illustrate that this new extension of ALMO-EDA provides a valuable means to unravel the nature of intermolecular interactions and quantify their impacts on chemical reactivity in solution.

The AlkB family of non-heme-Fe(II)/2-oxoglutarate(2OG)-dependent oxygenases are essential regulators of RNA epigenetics by serving as erasers of one-carbon marks on RNA with release of formaldehyde (FA). Two major human AlkB family members, FTO and ALKBH5, both act as oxidative demethylases of N6 methyladenosine (m6A) but furnish different major products, N6 hydroxymethyladenosine (hm6A) and adenosine (A), respectively. Here we identify foundational mechanistic differences between FTO and ALKBH5 that promote these distinct biochemical outcomes. In contrast to FTO, which follows a traditional oxidative N-demethylation pathway to catalyze conversion of m6A to hm6A with subsequent slow release of A and FA, we find that ALKBH5 catalyzes a directm6A-to-A transformation with rapid FA release. We identify a catalytic R130/K132/Y139 triad within ALKBH5 that facilitates release of FA via an unprecedented covalent-based demethylation mechanism with direct detection of a covalent intermediate. Importantly, a K132Q mutant furnishes an ALKBH5 enzyme with an m6A demethylation profile that resembles that of FTO, establishing the importance of this residue in the proposed covalent mechanism. Finally, we show that ALKBH5 is an endogenous source of FA in the cell by activity-based sensing of FA fluxes perturbed via ALKBH5 knockdown. This work provides a fundamental biochemical rationale for non-redundant roles of these RNA demethylases beyond different substrate preferences and cellular localization, where m6A demethylation by ALKBH5 versus FTO results in release of FA, an endogenous one-carbon unit but potential genotoxin, at different rates in living systems.Significance StatementNon-heme iron enzymes FTO and ALKBH5 play central roles in epigenetic RNA regulation by catalyzing the oxidation of N6-methyladenosine (m6A) to produce N6-hydroxymethyladenosine (hm6A) and adenosine (A), respectively. Here, we provide a mechanistic rationale for these distinct biochemical outcomes by identifying that ALKBH5 performs m6A demethylation via an unprecedented covalent-based mechanism with concomitant and rapid release of A and formaldehyde (FA), whereas FTO liberates hm6A to release A and FA over longer timescales. This work reveals foundational biochemical differences between these closely related but non-redundant epigenetic enzymes and identifies ALKBH5 as an endogenous source of rapid formaldehyde generation in cells.

Background Optimal fluid management in patients with COVID-19 has not been reported. This retrospective, multicenter study investigated the impact of intravenous infusion volume in the early stage of COVID-19 on clinical outcomes. Methods 127 patients from two tertiary hospitals were separated into the “conservative” and “liberal” groups based on average daily intravenous infusion volume within the first seven days after admission. Basic information, demographic and epidemiological characteristics, laboratory findings, treatments, and outcome measures were retrieved from medical records. The disease progression and prognosis were analyzed and compared. Results The average daily intravenous infusion volume within 7 days was 500 (150–700) ml/day in the conservative-strategy group (n = 87), and 1100 (1000–1288) ml/day in the liberal-strategy group (n = 40) (p p > 0.05). The final K+ in the liberal group was slightly higher than that at admission, and the final hematocrit level in the conservative group had a significant difference than that at admission (p p = 0.120). However, compared to the liberal group, conservative group had statistically lower rates of disease progression (9.3% vs 37.5%, p p p = 0.012). Conclusions Although there appeared to be no significant difference in the duration of hospitalization between using conservative and liberal fluid management strategies, the former was associated with lower rates of disease progression, mechanical ventilation and in-hospital mortality without increased nonpulmonary-organ dysfunction. These results support the importance of implementing conservative intravenous fluid infusion in the early stage of COVID-19.

Carbon monoxide (CO) is an emerging gasotransmitter and reactive carbon species with broad anti-inflammatory, cytoprotective, and neurotransmitter functions along with therapeutic potential for the treatment of cardiovascular diseases. The study of CO chemistry in biology and medicine relative to other prominent gasotransmitters such as NO and H2S remains challenging, in large part due to limitations in available tools for the direct visualization of this transient and freely diffusing small molecule in complex living systems. Here we report a ligand-directed activity-based sensing (ABS) approach to CO detection through palladium-mediated carbonylation chemistry. Specifically, the design and synthesis of a series of ABS probes with systematic alterations in the palladium-ligand environment (e.g., sp3-S, sp3-N, sp2-N) establish structureactivity relationships for palladacycles to confer selective reactivity with CO under physiological conditions. These fundamental studies led to the development of an optimized probe, termed Carbon Monoxide Probe-3 Ester Pyridine (COP3E-Py), which enables imaging of CO release in live cell and brain settings, including monitoring of endogenous CO production that triggers presynaptic dopamine release in fly brains. This work provides a unique tool for studying CO in living systems and establishes the utility of a synthetic methods approach to activity-based sensing using principles of organometallic chemistry

Type I interferons (IFN-Is) are a very important group of cytokines that are produced by innate immune cells but also act on adaptive immune cells. IFN-Is possess antiviral, antitumor, and anti-proliferative effects, as well are associated with the initiation and maintenance of autoimmune disorders. Studies have shown that aberrantly expressed IFN-Is and/or type I IFN-inducible gene signatures in the serum or tissues of patients with autoimmune disorders are linked to their pathogenesis, clinical manifestations, and disease activity. Type I interferonopathies with mutations in genes impacting the type I IFN signaling pathway have shown symptoms and characteristics similar to those of systemic lupus erythematosus (SLE). Furthermore, both interventions in animal models and clinical trials of therapies targeting the type I IFN signaling pathway have shown efficacy in the treatment of autoimmune diseases. Our review aims to summarize the functions and targeted therapies (as well as clinical trials) of IFN-Is in both adult and pediatric autoimmune diseases, such as SLE, pediatric SLE (pSLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), Sjogren syndrome (SjS), and systemic sclerosis (SSc), discussing the potential abnormal regulation of transcription factors and epigenetic modifications and providing a potential mechanism for pathogenesis and therapeutic strategies for future clinical use.

Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease that is characterized by dysregulated dendritic cells, T and B cells, and abundant autoantibodies. The pathogenesis of lupus remains unclear. However, increasing evidence has shown that environment factors, genetic susceptibilities, and epigenetic regulation contribute to abnormalities in the immune system. In the past decades, several risk gene loci have been identified, such as MHC and C1q. However, genetics cannot explain the high discordance of lupus incidence in homozygous twins. Environmental factor-induced epigenetic modifications on immune cells may provide some insight. Epigenetics refers to inheritable changes in a chromosome without altering DNA sequence. The primary mechanisms of epigenetics include DNA methylation, histone modifications, and non-coding RNA regulations. Increasing evidence has shown the importance of dysregulated epigenetic modifications in immune cells in pathogenesis of lupus, and has identified epigenetic changes as potential biomarkers and therapeutic targets. Environmental factors, such as drugs, diet, and pollution, may also be the triggers of epigenetic changes. Therefore, this chapter will summarize the up-to-date progress on epigenetics regulation in lupus, in order to broaden our understanding of lupus and discuss the potential roles of epigenetic regulations for clinical applications.

Food allergy is a global health problem, particularly in developed countries. It is mainly mediated by Th2 cell and IgE produced by B cells. While the pathogenesis of IgE-mediated food allergy is quite straightforward, the factors that lead to the development of food allergies at any age in children and adults are unclear. Recent studies have revealed that genetics, epigenetics, and environmental exposures contribute to the development of atopy. In this chapter, we discuss the interplay between these three key elements, reveal how epigenetic modifications may mediate genetic susceptibility of food allergies, and explain why epigenetic modifications may be the key in environmental factors mediated-gene expression, leading to the loss of immune tolerance and eventually, the initiation of food allergies. It should be noted that the study of the role of epigenetics in food allergy is still in its infancy, and lags behind research on epigenetics in other fields such as cancer and autoimmune diseases. One of the reasons for this may be the extreme complexity and variability of clinical presentation of food allergy, ranging from less severe forms such as oral allergy syndrome to full-blown anaphylaxis. Research on early exposure has disrupted the previous thinking of avoidance of food allergies to prevent sensitization in children, instead leading to recommendations that early introduction to foods may, in fact, induce tolerance. However, clear and unequivocal guidelines on how to approach this in the clinical setting have not been developed. The coming of the epigenetic era in food allergies is to provide better understanding of pathogenesis of food allergy, as well as providing therapeutic and preventive strategies for this very common condition.

Type 1 diabetes (T1D) is an autoimmune disease caused by the interaction between genetic alterations and environmental factors. More than 60 susceptible genes or loci of T1D have been identified. Among them, HLA regions are reported to contribute about 50% of genetic susceptibility in Caucasians. There are many environmental factors involved in the pathogenesis of T1D. Environmental factors may change the expression of genes through epigenetic mechanisms, thus inducing individuals with susceptible genes to develop T1D; however, the underlying mechanisms remain poorly understood. The major epigenetic modifications include DNA methylation, histone modification, and non-coding RNA. There has been extensive research on the role of epigenetic mechanisms including aberrant DNA methylation, histone modification, and microRNA in the pathogenesis of T1D. DNA methylation and microRNA have been proposed as biomarkers to predict islet β cell death, which needs further confirmation before any clinical application can be developed. Small molecule inhibitors of histone deacetylases, histone methylation, and DNA methylation are potentially important for preventing T1D or in the reprogramming of insulin-producing cells. This chapter mainly focuses on T1D-related DNA methylation, histone modification, and non-coding RNA, as well as their possible translational potential in the early diagnosis and treatment of T1D.

Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence. Disruption of gene expression patterns which are governed by epigenetics can result in autoimmune diseases, cancers, and various other maladies. Mechanisms of epigenetics include DNA methylation (and demethylation), histone modifications, and non-coding RNAs such as microRNAs. Compared to numerous studies that have focused on the field of genetics, research on epigenetics is fairly recent. In contrast to genetic changes, which are difficult to reverse, epigenetic aberrations can be pharmaceutically reversible. The emerging tools of epigenetics can be used as preventive, diagnostic, and therapeutic markers. With the development of drugs that target the specific epigenetic mechanisms involved in the regulation of gene expression, development and utilization of epigenetic tools are an appropriate and effective approach that can be clinically applied to the treatment of various diseases.

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.

We present a bioinspired strategy for enhancing electrochemical carbon dioxide reduction catalysis by cooperative use of base-metal molecular catalysts with intermolecular second-sphere redox mediators that facilitate both electron and proton transfer. Functional synthetic mimics of the biological redox cofactor NADH, which are electrochemically stable and are capable of mediating both electron and proton transfer, can enhance the activity of an iron porphyrin catalyst for electrochemical reduction of CO2 to CO, achieving a 13-fold rate improvement without altering the intrinsic high selectivity of this catalyst platform for CO2 versus proton reduction. Evaluation of a systematic series of NADH analogs and redox-inactive control additives with varying proton and electron reservoir properties reveals that both electron and proton transfer contribute to the observed catalytic enhancements. This work establishes that second-sphere dual control of electron and proton inventories is a viable design strategy for developing more effective electrocatalysts for CO2 reduction, providing a starting point for broader applications of this approach to other multi-electron, multi-proton transformations.

Corticosteroid associated osteonecrosis is bone death resulting from the use of chronic glucocorticoids and most commonly affects the femoral head, although the bones such as around knee joint, wrist joint and ankle joint can be affected. The pathogenesis is likely multifactorial, with genetic and environmental factors playing a role. Epigenetics may be the mechanism by which environment exerts it effects. In spite of recent discoveries, the exact pathogenesis of corticosteroid associated osteonecrosis is unknown. Over the past few years, more miRNA's have been found to be associated with osteonecrosis. The older mechanisms such as a coagulopathy, abnormalities in apoptosis and lipid metabolism dysfunction are still believed to play a role. The role of inflammatory pathways including the PDK1/AKT/mTOR signaling pathway, the PERK and Parkin pathways have been increasingly recognized as playing a mechanistic role. Histological damage to the joint can occur before the presence of symptoms. The most common symptoms are pain and an inability to bear weight. Differential diagnosis includes infection, bone marrow edema syndrome or subchondral fracture. Early detection is important for successful management of the condition. MRI is the best radiologic technique to diagnosis femoral head osteonecrosis. Multiple staging systems for osteonecrosis have been used over the years, including the Ficat and Arlet system and the Steinberg criteria. The later stages of these staging systems are irreversible. Both non-surgical (conservative) and surgical modes of therapy are used in the treatment of osteonecrosis.