Vulnerable brain regions in adolescent major depressive disorder: A resting-state functional magnetic resonance imaging activation likelihood estimation meta-analysis.

BACKGROUND: Adolescent major depressive disorder (MDD) is a significant mental health concern that often leads to recurrent depression in adulthood. Resting-state functional magnetic resonance imaging (rs-fMRI) offers unique insights into the neural mechanisms underlying this condition. However, despite previous research, the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated. AIM: To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation (ALE) meta-analysis. METHODS: We performed a comprehensive literature search through July 12, 2023, for studies investigating brain functional changes in adolescent MDD patients. We utilized regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) analyses. We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls (HCs) using ALE. RESULTS: Ten studies (369 adolescent MDD patients and 313 HCs) were included. Combining the ReHo and ALFF/fALFF data, the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs (voxel size: 648 mm3, P < 0.05), and no brain region exhibited increased activity. Based on the ALFF data, we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients (voxel size: 736 mm3, P < 0.05), with no regions exhibiting increased activity. CONCLUSION: Through ALE meta-analysis, we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients, increasing our understanding of the neuropathology of affected adolescents.

Alterations of sleep deprivation on brain function: A coordinate-based resting-state functional magnetic resonance imaging meta-analysis.

BACKGROUND: Sleep deprivation is a prevalent issue that impacts cognitive function. Although numerous neuroimaging studies have explored the neural correlates of sleep loss, inconsistencies persist in the reported results, necessitating an investigation into the consistent brain functional changes resulting from sleep loss. AIM: To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases. Two meta-analytic methods, signed differential mapping (SDM) and activation likelihood estimation (ALE), were employed to analyze functional magnetic resonance imaging (fMRI) data. METHODS: A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29, 2023. Studies that met specific inclu-sion criteria, focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered. A total of 21 studies were selected for SDM and ALE meta-analyses. RESULTS: Twenty-one studies, including 23 experiments and 498 subjects, were included. Compared to pre-sleep deprivation, post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule. SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus, left middle frontal gyrus, corpus callosum, and right cuneus. CONCLUSION: This meta-analysis consistently identified brain regions affected by sleep deprivation, notably the left medial frontal gyrus and corpus callosum, shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.

Cayratia albifolia C.L.Li exerts anti-rheumatoid arthritis effect by inhibiting macrophage activation and neutrophil extracellular traps (NETs).

BACKGROUND: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. RESULTS: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. CONCLUSIONS: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

Negative serum (1,3) -ß-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR.

OBJECTIVE: The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results. METHODS: This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort. RESULTS: Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG. CONCLUSIONS: Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Irisin alleviates hyperoxia-induced bronchopulmonary dysplasia through activation of Nrf2/HO-1 pathway.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common pulmonary injury among premature infants, which is often caused by hyperoxia exposure. Irisin is a novel hormone-like myokine derived mainly from skeletal muscles as well as adipose tissues. Many studies have indicated that Irisin exert a variety of properties against hyperoxia-induced inflammation and oxidative stress (OS). We aimed to evaluate the effects of irisin on hyperoxia-induced lung injury explore the underlying mechanisms. METHODS: BPD model was established after exposing newborn mouse to 85% oxygen. BPD mouse received continuous intraperitoneal injection of irisin at a dose of 25 µg/kg/day. Lung tissues were collected for histological examination at 7 and 14 days after birth. The alveolarization and alveolar vascularization of each animal was assessed. Levels of oxidative stress indicators, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were detected at 14 days after birth. RESULTS: Hyperoxia exposure induced a markedly alveolar simplification and a disrupted alveolar angiogenesis, which was ameliorated by irisin treatment. The hyperoxia-induced increase in these oxidative stress indicators was significantly reversed by irisin treatment. The Nrf2/HO-1 pathway is inducted in the hyperoxia-induced BPD mouse model, which is further activated by irisin treatment. CONCLUSION: Our results demonstrated the beneficial effects of irisin in reducing the OS, enhancing alveolarization, and promoting vascular development through activation of Nrf2/HO-1 axis in a hyperoxia-induced experimental model of BPD.

Lycorine promotes IDH1 acetylation to induce mitochondrial dynamics imbalance in colorectal cancer cells.

Isocitrate dehydrogenase (IDH) 1 and 2, as essential enzymes in energy metabolism, contribute to the survival and drug resistance of a variety of solid tumors, especially for colorectal cancer (CRC). However, the underlying molecular mechanism still remains unclear. In this study, IDH1 was identified as a crucial cellular target of a natural-derived anti-CRC small molecule lycorine, using the unbiased thermal proteome profiling (TPP) strategy. We found that lycorine directly targeted a unique C-terminal domain of IDH1, and disrupted IDH1 interaction with deacetylase sirtuin 1 (SIRT1), thereby significantly promoting IDH1 acetylation modification. Then, lycorine noticeably triggered oxidative stress in CRC cells to cause mitochondrial membranes injury, and subsequently facilitated mitochondrial fission. Specific knockdown of IDH1 or SIRT1 markedly aggrieved lycorine-mediated oxidative stress and mitochondrial fragmentation in CRC cells. Furthermore, the combination of lycorine and sirtuins blocker nicotinamide (NAM) exhibited a synergic therapeutic effect in CRC cells. Collectively, our results reveal that IDH1 may serve as a promising therapeutic target for CRC via pharmacologically driving oxidative stress-dependent mitochondrial dynamics imbalance.

Value of red blood cell distribution width in prediction of diastolic dysfunction in cirrhotic cardiomyopathy.

BACKGROUND: Clinical diagnosis of cirrhotic cardiomyopathy (CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failure. AIM: To explore suitable biomarkers for early CCM prediction. METHODS: A total of 505 eligible patients were enrolled in this study and divided into four groups according to Child-Pugh classification: Group I, Class A without CCM (105 cases); Group II, Class A with CCM (175 cases); Group III, Class B with CCM (139 cases); and Group IV, Class C with CCM (86 cases). Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine whether red blood cell distribution width (RDW) was an independent risk factor for CCM risk. The relationships between RDW and Child-Pugh scores, Model for End-Stage Liver Disease (MELD) scores, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed by Pearson correlation analysis. RESULTS: A constant RDW increase was evident from Group I to Group IV (12.54 ± 0.85, 13.29 ± 1.19, 14.30 ± 1.96, and 16.25 ± 2.13, respectively). Pearson correlation analysis showed that RDW was positively correlated with Child-Pugh scores (r = 0.642, P < 0.001), MELD scores (r = 0.592, P < 0.001), and NT-proBNP (r = 0.715, P < 0.001). Furthermore, between Group I and Group II, RDW was the only significant index (odds ratio: 2.175, 95% confidence interval [CI]: 1.549-3.054, P < 0.001), and it reached statistical significance when examined by ROC curve analysis (area under the curve: 0.686, 95%CI: 0.624-0.748, P < 0.001). CONCLUSION: RDW can serve as an effective and accessible clinical indicator for the prediction of diastolic dysfunction in CCM, in which a numerical value of more than 13.05% may indicate an increasing CCM risk.

Allosteric Activation of Transglutaminase 2 via Inducing an "Open" Conformation for Osteoblast Differentiation.

Osteoblasts play an important role in the regulation of bone homeostasis throughout life. Thus, the damage of osteoblasts can lead to serious skeletal diseases, highlighting the urgent need for novel pharmacological targets. This study introduces chemical genetics strategy by using small molecule forskolin (FSK) as a probe to explore the druggable targets for osteoporosis. Here, this work reveals that transglutaminase 2 (TGM2) served as a major cellular target of FSK to obviously induce osteoblast differentiation. Then, this work identifies a previously undisclosed allosteric site in the catalytic core of TGM2. In particular, FSK formed multiple hydrogen bonds in a saddle-like domain to induce an "open" conformation of the ß-sandwich domain in TGM2, thereby promoting the substrate protein crosslinks by incorporating polyamine. Furthermore, this work finds that TGM2 interacted with several mitochondrial homeostasis-associated proteins to improve mitochondrial dynamics and ATP production for osteoblast differentiation. Finally, this work observes that FSK effectively ameliorated osteoporosis in the ovariectomy mice model. Taken together, these findings show a previously undescribed pharmacological allosteric site on TGM2 for osteoporosis treatment, and also provide an available chemical tool for interrogating TGM2 biology and developing bone anabolic agent.

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy.

Lymphoma, which is highly malignant, stems from lymph nodes and lymphoid tissue. Lymphoma cells express programmed death-ligand 1/2 (PD-L1/PD-L2), which binds with programmed cell death 1 protein (PD-1) to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance. Recently, immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors (nivolumab and pembrolizumab) have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients. Accordingly, the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually, which results in an increasing number of patients developing immune-related adverse events (irAEs). The occurrence of irAEs inevitably affects the benefits provided by immunotherapy, particularly when PD-1 inhibitors are applied. However, the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation. This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors. A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

[Expression level and clinical significance of CD44 and CD33 in 77 patients with benign lymphoadenosis of oral mucosa].

PURPOSE: To investigate the expression and clinical significance of CD44 and CD33 in benign lymphoadenosis of oral mucosa(BLOM). METHODS: From January 2017 to March 2020, seventy-seven BLOM wax blocks from the Department of Pathology of Qingdao Traditional Chinese Medicine Hospital were selected as the experimental group, and 63 cases of normal oral mucosal tissue wax blocks during the same period were selected as the control group. Immunohistochemical method was used to detect the positive expression of CD44 and CD33 in the two groups.Spearman correlation analysis was used to analyze the correlation between the positive expression of CD33 and the positive expression of CD44 in the diseased tissues of BLOM patients.The general information about patients were collected.The relationship between the expression of CD33 and CD44 in the diseased tissues of BLOM patients and the clinicopathological characteristics of BLOM patients were analyzed. SPSS 21.0 software package was used for statistical analysis of the data. RESULTS: The positive expression rates of CD33 in the control group and the experimental group were 95.24% and 63.64%, respectively, and the difference was statistically significant(P＜0.05). The positive expression rates of CD44 in the control group and the experimental group were 93.65% and 67.53%, respectively, and the difference was statistically significant(P＜0.05). The results of Spearman correlation analysis showed that the positive expression of CD33 in the diseased tissues of BLOM patients was positively correlated with the positive expression of CD44 (r=0.834, P=0.002). The expression of CD33 and CD44 in the diseased tissues of patients with BLOM were related to clinical type, degree of inflammation, presence or absence of lymphoid follicles, and lymphocyte infiltration(P＜0.05), but not related to age, gender, course of disease, location, and epithelial surface keratinization(P＞0.05). CONCLUSIONS: The positive expression rate of CD33 and CD44 in the BLOM tissues decreased, which was closely related to the clinical type, degree of inflammation, presence or absence of lymphoid follicles, and lymphocyte infiltration.

Inhibition of human sulfotransferases (SULTs) by per- and polyfluoroalkyl substances (PFASs) and structure-activity relationship.

Per- and polyfluoroalkyl substances (PFASs) are a family of highly fluorinated aliphatic substances widely used in industrial and commercial applications. This study aims to determine the inhibition of PFASs towards sulfotransferases (SULTs) activity, and trying to explain the toxicity mechanism of PFASs. In vitro recombinant SULTs-catalyzed sulfation of p-nitrophenol (PNP) was utilized as a probe reaction. The incubation system was consisted of PFASs, SULTs, PNP, 3'-phosphoadenosine-5'-phosphosulfate, MgCl2 and Tris-HCl buffer. Ultra-performance liquid chromatography was employed for analysis of the metabolites. All tested PFASs showed inhibition towards SULTs. The longer the carbon chain length of the PFASs terminated with -COOH, the higher is its capability of inhibiting SULT1A3. PFASs with -SO3H had a relatively higher ability to inhibit SULT1A3 activity than those with -COOH, -I and -OH. The inhibition kinetic parameter was 2.16 and 1.42 µM for PFOS-SULT1A1, PFTA-SULT1B1. In vitro in vivo extrapolation showed that the concentration of PFOS and PFTA in human matrices might be higher than the threshold for inducing inhibition of SULTs. Therefore, PFASs could interfere with the metabolic pathways catalyzed by SULTs in vivo. All these results will help to understand the toxicity of PFASs from the perspective of metabolism.

Immunological Findings in a Group of Individuals Who Were Poor or Non-Responders to Standard Two-Dose SARS-CoV-2 Vaccines.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic. However, data on the poor or non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of this study was to comprehensively compare the immunological characteristics of poor or non-responders to SARS-CoV-2 vaccines in the 18-59-year group with those in the ≥60-year group using internationally recognized cut-off values. The main outcome was effective seroconversion characterized by an anti-SARS-CoV-2 spike IgG level of at least a four-fold increase from baseline. Profiling of naïve immune cells was analyzed prior to vaccination to demonstrate baseline immunity. The outcomes of effective seroconversion in patients aged 18-59 years with those in patients aged ≥60 years were compared. The quantitative level of anti-spike IgG was significantly lower in individuals aged ≥60 and men aged 18-59 years. There were 7.5% of poor or non-responders among the 18-59 years and 11.7% of poor or non-responders in the ≥60 years using a four-fold increase parameter. There were 37.0-58.1% with low lymphocyte count (<1000/mm3), 33.3-45.2% with low CD4 cell counts (<500/mm3), and 74.1-96.8% with low B cell counts (<100/mm3) in the non-seroconversion group. An individual with an anti-SARS-CoV-2 spike IgG titer below 50 BAU/mL might be considered a poor or non-responder between 14 and 90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended to poor or non-responders as soon as possible to reduce disease severity and mortality.

Inherent Capability of Self-Assembling Nanostructures in Specific Proteasome Activation for Cancer Cell Pyroptosis.

Understanding the direct interaction of nanostructures per se with biological systems is important for biomedical applications. However, whether nanostructures regulate biological systems by targeting specific cellular proteins remains largely unknown. In the present work, self-assembling nanomicelles are constructed using small-molecule oleanolic acid (OA) as a molecular template. Unexpectedly, without modifications by functional ligands, OA nanomicelles significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanism study reveals that OA nanomicelles interact with PSMA6 to dynamically modulate its N-terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome. Subsequently, OA nanomicelles accelerate the degradation of several crucial proteins, thus potently driving cancer cell pyroptosis. For translational medicine, OA nanomicelles exhibit a significant anticancer potential in tumor-bearing mouse models and stimulate immune cell infiltration. Collectively, this proof-of-concept study advances the mechanical understanding of nanostructure-guided biological effects via their inherent capacity to activate proteasome.

[Comparative analysis of powder and piece decocting processes of Yinqiao Powder based on determination of multiple primary components].

The present study established specific chromatograms and a method for determining multiple primary components in Yinqiao Powder decoctions and compared the change rules of chemical composition in powder and piece decocting processes of Yinqiao Powder to provide a scientific basis for the modern research of preparations of Yinqiao Powder. Powder and piece decoctions of Yinqiao Powder were prepared. The specific chromatograms were determined and the content of 17 primary components was measured by high-performance liquid chromatography(HPLC), including adoxosidic acid, neochlorogenic acid, forsythoside E, loganic acid, chlorogenic acid, cryptochlorogenic acid, sweroside, forsythoside Ⅰ, forsythoside H, forsythoside A, isochlorogenic acid B, E-aldosecologanin, hesperidin, phillyrin, arctiin, liquiritigenin, and dipotassium glycyrrhizinate. The effect of decocting time on the chemical composition in powder and piece decoctions of Yinqiao Powder was investigated. As a result, the specific chromatogram similarities of powder decoctions of Yinqiao Powder with different decocting time were high, which indicated that their chemical compositions were similar, while the similarities of piece decoctions were low, suggesting similar chemical compositions with big differences. In powder decoctions, the concentrations of neochlorogenic acid, cryptochlorogenic acid, forsytherin H, and isochlorogenic acid B increased with the prolongation of decocting time, and those of adoxosidic acid, forsythoside E, forsythoside Ⅰ, E-aldosecologanin, phillyrin, dipotassium glycyrrhizinate, loganic acid, arctiin, sweroside, and liquiritigenin increased firstly and tended to be stable, while those of forsythoside A, chlorogenic acid, and hesperidin increased firstly and then decreased. In piece decoctions, the concentration of chlorogenic acid increased firstly and then decreased with the prolongation of decocting time, while those of the remaining 16 components showed an upward trend. The concentrations of adoxosidic acid, forsythoside E, forsythoside Ⅰ, E-aldosecologanin, phillyrin, dipotassium glycyrrhizinate, forsythoside A, forsythoside H, and chlorogenic acid in powder decoctions were higher than those in piece decoctions. The concentrations of hesperidin, loganic acid, phillyrin, sweroside, liquiritigenin, neochlorogenic acid, and cryptochlorogenic acid in powder decoctions were higher than those in piece decoctions within 40 min of decocting. The concentration of isochlorogenic acid B in powder decoctions was lower than that in piece decoction 10 min after decocting. The results showed that the decocting time and particle size of raw medicinal materials had certain effects on the content of chemical components in decoctions of Yinqiao Powder. Compared with the piece decocting, the powder decocting could achieve faster resolution of chemical components and higher concentrations, which confirmed the scientific evidence of the traditional powder decocting method of Yinqiao Powder. For the piece decocting of prescriptions of Yinqiao Powder, extraction time should be prolonged and extraction times should be increased to achieve the same effect as the powder decocting.

Immunological findings in a group of individuals who were non-responders to standard two-dose SARS-CoV-2 vaccines

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic. The virus has infected more than 505 million people and caused more than 6 million deaths. However, data on non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of the study is to comprehensively compare the immunological characteristics of non-responders to SARS-CoV-2 vaccines in the 18-59 years with that in the 60 years and older using internationally recognized cutoff values. Participants included 627 individuals who received physical examinations and volunteered to participate in COVID-19 vaccination from the general population. The main outcome was an effective seroconversion characterized by anti-SARS-CoV-2 spike IgG level of at least 4-fold increase from baseline. Profiling of naive immune cells was analyzed prior to vaccination to demonstrate baseline immunity. Outcomes of effective seroconversion in the 18-59 years with that in the 60 years and older were compared. The quantitative level of the anti-spike IgG was significantly lower in the 60 years and older and in men among the 18-59 years. There were 7.5% of non-responders among the 18-59 years and 11.7% of non-responders in the 60 years and older using the 4-fold increase parameter. The effective seroconversion rate was significantly related to the level of certain immune cells before vaccination, such as CD4 cells, CD8 cells and B cells and the age. An individual with a titer of anti-SARS-CoV-2 spike IgG that is below 50 BAU/mL might be considered a non-responder between 14-90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended for non-responders as soon as possible to reduce disease severity and mortality.

Late-Onset Bartter Syndrome Type II Due to a Novel Compound Heterozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review.

Background: Bartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle's loop. BS type II is typically considered as a disorder of infancy and seldom seen in adults. Case Presentation: A 34-year-old woman was admitted with generalized body numbness and hand convulsions, without growth retardation. Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. She was misdiagnosed during the initial diagnosis process and was finally diagnosed with late-onset BS type II via genetic testing through next-generation sequencing combined with Sanger sequencing. A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene from her parents was identified and speculated to be a potential pathogenic gene variation. Conclusion: We report a case of late-onset BS type II with a novel compound heterozygous mutation in KCNJ1. Both variants are novel and have never been reported. Our report will have a significant impact on the diagnosis of BS in other patients without typical clinical presentations and emphasizes the importance of genetic investigation.

Photoaffinity Labeling-Based Chemoproteomic Strategy Reveals RBBP4 as a Cellular Target of Protopanaxadiol against Colorectal Cancer Cells.

Protopanaxadiol (PPD), a main ginseng metabolite, exerts powerful anticancer effects against multiple types of cancer; however, its cellular targets remain elusive. Here, we synthesized a cell-permeable PPD probe via introducing a bifunctional alkyne-containing diazirine photo-crosslinker and performed a photoaffinity labeling-based chemoproteomic study. We identified retinoblastoma binding protein 4 (RBBP4), a chromatin remodeling factor, as an essential cellular target of PPD in HCT116 colorectal cancer cells. PPD significantly decreased RBBP4-dependent trimethylation at lysine 27 of histone H3 (H3K27me3), a crucial epigenetic marker that correlates with histologic signs of colorectal cancer aggressiveness, and PPD inhibition of proliferation and migration of HCT116 cells was antagonized by RBBP4 RNA silencing. Collectively, our study highlights a previously undisclosed anti-colorectal cancer cellular target of the ginseng metabolite and advances the fundamental understanding of RBBP4 functions via a chemical biology strategy.

Interpretation of non-responders to SARS-CoV-2 vaccines using WHO International Standard

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with more than 485 millions infected. Questions about non-responders to SARS-CoV-2 vaccines remain unaddressed. Here, we report data from people after administering the complete dose of SARS-CoV-2 vaccines using the World Health Organization International Standard for anti-SARS-CoV-2 immunoglobulin. Our study showed that immune cells such as CD4 cells, CD8 cells, and B cells and anti-spike immunoglobulin G levels were significantly reduced in the elderly. There were 7.5% non-responders among the 18-59 yr group and 11.7% in the [≥]60 yr group. A titer of anti-SARS-CoV-2 spike immunoglobulin G is blew 50 BAU/mL to be considered as non-responders at intervals of 30 to 90 days after the last vaccine dose. Booster vaccination may be recommended for non-responders to reduce the disease severity and mortality.