Acquired methemoglobinemia in a third trimester puerpera and her premature infant with sodium nitrite poisoning: A case report.

BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

Carbon dots for efficient detection of water content in organic solvents.

The trace amount of water in organic solvents can affect the progress of chemical reactions, which will adversely affect chemical production in many industries, resulting in a doubling of costs. In this work, carbon dots (CDs) with abundant polar groups were synthesized by a simple one-step hydrothermal method. The prepared CDs showed superior dispersibility and fluorescence performance compared to the CDs that have been reported for the detection of water content in organic solvents. It can realize the fluorescence detection of trace water in several water-soluble organic solvents such as N,N-dimethylformamide, ethanol and methanol with wide linear range (0 %-100 %) and high sensitivity. This will provide a powerful tool for the rapid detection of water content in organic solvents in chemical production.

Covalent post-synthetic modification of MOFs as a fluorescent sensor for the efficient detection of the biomarker of cystinuria.

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal-organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence "turn-on" response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6-350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases.

PyBox-La(OTf)3-Catalyzed Enantioselective Diels-Alder Cycloadditions of 2-Alkenoylpyridines with Cyclopentadiene.

The PyBox-La(OTf)3-catalyzed enantioselective Diels-Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.

Integrating plasma proteome with genome reveals novel protein biomarkers in colorectal cancer.

BACKGROUND: Biomarkers for colorectal cancer (CRC) can complement population screening methods, but so far, few plasma proteins have been identified as biomarkers for CRC. This study aims to identify potential protein biomarkers and therapeutic targets for CRC within the proteome range. METHODS: We extracted summary-level data of circulating protein from 7 published genome-wide association studies (GWASs) of plasma proteome for Mendelian randomization (MR), summary-data-based MR (SMR), and co-localization analyses to screen and validate proteins with causal effects in CRC. In addition, we further conducted druggability evaluation, prognosis analysis at the transcriptional level, and enrichment expression at the single-cell level, highlighting the important role of these plasma protein biomarkers in CRC. RESULTS: We identified 117 plasma protein biomarkers associated with CRC risk, with 9 proteins showing stronger genetic correlations in Bayesian co-localization (PP.H4 > 0.70). Further, we found 26 protein-coding genes already used in targeted drug development and may potentially become therapeutic targets for CRC. In prognosis analysis, the encoding genes of plasma proteins exhibited consistent effects with MR analysis and can serve as prognostic biomarkers for CRC. Additionally, we also found that the differentially expressed proteins are mainly expressed in fibroblasts, endothelial cells, macrophages, and T cells. CONCLUSION: Our study has identified plasma protein biomarkers associated with CRC risk, which may complement population screening methods for CRC and achieve more precise treatment for patients.

In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection.

Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

Double-strand-break repair protein rad21 homolog/Synaptotagmin-7 alleviates Alzheimer's disease in mice by promoting M2 polarization of microglia.

Synaptotagmin-7 (SYT7) has been proposed as an innovative therapeutic strategy for treating cognitive impairment, while its contribution to Alzheimer's disease (AD) alleviation remains unclear. In this study, we investigated the role and potential mechanisms of SYT7 in AD. APP/PS1 mice were induced as an AD mouse model, and RNA-sequencing was conducted to analyze the transcriptomic differences between the brain tissues of AD mice and controls. SYT7, which was the most significantly differentially expressed gene in the RNA-sequencing, was found to be reduced in AD-like mice, and overexpression of SYT7 alleviated cognitive dysfunction and attenuated neuroinflammation and neuronal loss in the hippocampal tissues of mice with AD. Transcription factor double-strand-break repair protein rad21 homolog (RAD21) bound to the promoter of SYT7 to activate SYT7 transcription. SYT7 and RAD21 were expressed in microglia. SYT7 and RAD21 both promoted M2 polarization of microglia, while silencing of SYT7 repressed the M2 polarization of microglia in the presence of RAD21 overexpression. Overall, our results indicate that RAD21 mediated transcriptional activation of SYT7 to promote M2 polarization of microglia, thereby alleviating AD-like symptoms in mice, which might provide prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.

UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.

Background: Angiotensin (Ang)-II impairs the function of the antihypertensive enzyme ACE2 by promoting its internalization, ubiquitination and degradation thus contributing to hypertension. However, few ACE2 ubiquitination partners have been identified and their role in hypertension remains unknown. Methods: Proteomics and bioinformatic analysis were used to identify ACE2 ubiquitination partners in the brain, heart, and kidney from Ang-II-infused C57BL6/J mice from both sexes and validated the interaction between UBR1 and ACE2 in cells. Central and peripheral UBR1 knockdown was then performed in male mice to investigate its role in the maintenance of hypertension. Results: Proteomics analysis from hypothalamus identified UBR1 as a potential E3 ligase promoting ACE2 ubiquitination. Enhanced UBR1 expression, associated with ACE2 reduction, was confirmed in various tissues from hypertensive male mice and human samples. Treatment of endothelial and smooth muscle cells with testosterone, but not 17ß-estradiol, confirmed a sex-specific regulation of UBR1. In vivo silencing of UBR1 using chronic administration of small interference RNA resulted in the restoration of ACE2 levels in hypertensive males. A transient decrease in blood pressure following intracerebroventricular, but not systemic, infusion was also observed. Interestingly, UBR1 knockdown increased the brain activation of Nedd4-2, an E3 ligase promoting ACE2 ubiquitination and reduced expression of SGK1, the kinase inactivating Nedd4-2. Conclusions: These data demonstrate that UBR1 is a novel ubiquitin ligase targeting ACE2 in hypertension. UBR1 and Nedd4-2 E3 ligases appear to work synergistically to ubiquitinate ACE2. Targeting of these ubiquitin ligases may represent a novel strategy to restore ACE2 compensatory activity in hypertension.

Y(OTf)3-Salazin-Catalyzed Asymmetric Aldol Condensation.

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π-stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands.

MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites.

Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here, we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a unique kinesin-based mechanism for polarized transport of vesicles to dendrites.

Reaction of 1,3,5-Triazinanes with Phosphoryl Diazomethanes: Access to 5-Phosphoryl-1,2,3,4-tetrahydropyrimidines.

Conversion of 1,3,5-triazinanes into 5-phosporyl-1,2,3,4-tetrahydropyrimidines is achieved efficiently through the microwave-assisted reaction with phosphoryl diazomethanes. Both trialkyl and triaryl 1,3,5-triazinanes were converted by diazomethyldiarylphosphine oxides, dialkyl diazomethylphosphonates, and alkyl diazomethyl(aryl)phosphinates and functionalized simultaneously in good to excellent yields. The reaction is a sequence of 1,3,5-triazinane fragmentation, tandem nucleophilic addition of the generated formaldimines and phosphoryl diazomethanes, and final N,N-acetalization.

Recent Advances in π-Stacking Interaction-Controlled Asymmetric Synthesis.

The π-stacking interaction is one of the most important intramolecular and intermolecular noncovalent interactions in organic chemistry. It plays an important role in stabilizing some structures and transition states in certain reactions via both intramolecular and intermolecular interactions, facilitating different selectivities, such as chemo-, regio-, and stereoselectivities. This minireview focuses on the recent examples of the π-stacking interaction-controlled asymmetric synthesis, including auxiliary-induced asymmetric synthesis, kinetic resolution, asymmetric synthesis of helicenes and heterohelicenes, and multilayer 3D chiral molecules.

Predictive and Prognostic Potentials of Lymphocyte-C-Reactive Protein Ratio Upon Hospitalization in Adult Patients with Acute Pancreatitis.

Purpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP). Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups. Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization. Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.

Dynamic lymphocyte-CRP ratio as a predictor: a single-centre retrospective study on disease severity and progression in adult COVID-19 patients.

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

Gut Microbiota Dysbiosis and Inflammation Dysfunction in Late-Life Depression: An Observational Cross-Sectional Analysis.

Purpose: There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD. Methods: This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines. Results: Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs. Conclusion: This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD.

π-Stacking-Controlled Dearomatic Sulfur-Shifted Ene Reaction of Ketenes and Polycyclic Arylthiiranes: Access to Areno[d]-ε-thiolactones.

Electrophilic ring-expansion of polycyclic arylthiiranes and ketenes generated from alkoxy/aryloxyacetyl chlorides in the presence of triethylamine (TEA) is developed and provides a new strategy for the synthesis of areno[d]-ε-thiolactones, areno[d]thiepinones, directly without catalysts or additives. This strategy features atom- and step-economic one-pot characteristic via a tandem sequence of in situ ketene generation, π-stacking-controlled dearomatic sulfur-shifted ene, and aromatization. The current reaction is a novel strategy of electrophilic ring expansions of three-membered saturated heterocycles.

Tf2O/2-Chloropyridine-Triggered Synthesis of Benzo[b]thiophene 1,1-Dioxides from Sulfonium α-Acyl Sulfonylmethylides.

Triflic anhydride and 2-chloropyridine-comediated tandem activation, intramolecular aromatic electrophilic addition, and 1,2-sulfonyl shift via spirocyclic intermediates of sulfonium α-acyl sulfonylmethylides realize the efficient synthesis of 2-alkyl/arylthiobenzo[b]thiophene 1,1-dioxides. The deactivated sulfonyl group determines the site-selectivity of the electrophilic addition via the ipso-attack, while the following S-migration controls the regioselectivity. Some of 2-methylthiobenzo[b]thiophene 1,1-dioxides show fluorescence properties in the solid state and in their solutions.

Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress.

BACKGROUND: Agomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine's effects on catalase activity, oxidative stress, and inflammation. METHODS: Chronic restraint stress (CRS) model mice were established over 4 weeks, and AGO 50 mg/kg was administered to different groups alongside a deferasirox (DFX) 10 mg/kg gavage treatment. Behavioral tests were performed to assess the effect of AGO on the remission of depression-like behaviors. Meanwhile, the expression of CAT, the oxidative stress signaling pathway and inflammatory protein markers were assessed using ELISA, qRT-PCR, Western blot, and immunohistochemistry. RESULTS: Four weeks of AGO treatment significantly improved depression-like behavior in mice through the activation of catalase in the hippocampus and serum of the model mice, increased superoxide dismutase expression, reduced malondialdehyde expression, and reduced oxidative stress damage. Deferasirox was found to offset this therapeutic effect partially. In addition, the inflammatory pathway (including nuclear factor-κB and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) was not significantly altered. CONCLUSIONS: AGO can exert antidepressant effects by altering oxidative stress by modulating catalase activity.

Integrative Multiomics Profiling Unveils the Protective Function of Ulinastatin against Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis is an inflammatory bowel disease with multiple pathogeneses. Here, we aimed to study the therapeutic role of ulinastatin (UTI), an anti-inflammatory bioagent, and its associated mechanisms in treating colitis. Dextran sulfate sodium was administrated to induce colitis in mice, and a subgroup of colitis mice was treated with UTI. The gut barrier defect and inflammatory manifestations of colitis were determined via histological and molecular experiments. In addition, transcriptomics, metagenomics, and metabolomics were employed to explore the possible mechanisms underlying the effects of UTI. We found that UTI significantly alleviated the inflammatory manifestations and intestinal barrier damage in the mice with colitis. Transcriptome sequencing revealed a correlation between the UTI treatment and JAK-STAT signaling pathway. UTI up-regulated the expression of SOCS1, which subsequently inhibited the phosphorylation of JAK2 and STAT3, thus limiting the action of inflammatory mediators. In addition, 16S rRNA sequencing illustrated that UTI maintained a more stable intestinal flora, protecting the gut from dysbiosis in colitis. Moreover, metabolomics analysis demonstrated that UTI indeed facilitated the production of some bile acids and short-chain fatty acids, which supported intestinal homeostasis. Our data provide evidence that UTI is effective in treating colitis and support the potential use of UTI treatment for patients with ulcerative colitis.

Hollow Ni3S4@Co3S4 with core-satellite nanostructure derived from metal-organic framework (MOF)-on-MOF hybrids as an electrode material for supercapacitors.

Metal-organic frameworks (MOFs) have found wide applications in the field of supercapacitors due to their highly controllable porous structure, big specific surface area, and abundant chemical functional groups. MOF-on-MOF hybrids not only enhance the composition of MOFs (such as ligands and/or metal centers) but also provide greater structural diversity. By utilizing MOFs as precursors for preparing sulfides, the unique characteristics and inherent structure of MOFs are preserved but their conductivity and capacitance are enhanced. This study successfully synthesized hollow-structured Ni3S4@Co3S4 derived from an Ni-MOF@ZIF-67 hybrid structure, where the Ni-MOF serves as the core and ZIF-67 as the satellite. The Ni3S4@Co3S4 electrode demonstrated a specific capacity as high as 747.3 C g-1 at 1 A g-1, and it could still maintain 77% of its initial capacity at 10 A g-1. Furthermore, the assembled Ni3S4@Co3S4//AC hybrid supercapacitor (HSC) device achieved a maximum energy density of 30.8 W h kg-1 when the power density was 750 W kg-1. The device exhibited remarkable cycling durability, retaining 85.4% of its initial capacitance after 5000 cycles. Therefore, the derived functional materials based on MOF-on-MOF provide a more scalable and promising approach for the preparation of efficient electrode materials.