Boosting Propane Dehydrogenation by the Regioselective Distribution of Subnanometric CoO Clusters in MFI Zeolite Nanosheets.

Direct dehydrogenation of propane (PDH) has already been implemented worldwide in industrial processes to produce value-added propylene. The discovery of earth-abundant and environmentally friendly metal with high activity in C-H cleavage is of great importance. Co species encapsulated within zeolite are highly efficient for catalyzing direct dehydrogenation. However, exploring a promising Co catalyst remains a nontrivial target. Direct control of the regioselective distribution of Co species in the zeolite framework through altering their crystal morphology gives opportunities to modify the metallic Lewis acidic features, thus providing an active and appealing catalyst. Herein, we achieved the regioselective localization of highly active subnanometric CoO clusters in straight channels of siliceous MFI zeolite nanosheets with controllable thickness and aspect ratio. The subnanometric CoO species were identified by different types of spectroscopies, probe measurements, and density functional theory calculations, as the coordination site for the electron-donating propane molecules. The catalyst showed promising catalytic activity for the industrially important PDH with propane conversion of 41.8% and propylene selectivity higher than 95% and was durable during 10 successive regeneration cycles. These findings highlight a green and facile method to synthesize metal-containing zeolitic materials with regioselective metal distribution and also to open up a future perspectives for designing advanced catalysts with integrated advantages of the zeolitic matrix and metal structures.

Efficacy and Safety of Oral Herbal Drugs Used as Adjunctive Therapy for Melasma: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Melasma is an acquired disorder of facial pigmentation. Its etiology is multifactorial; thus, the management is usually challenging. As a complementary therapy, herbal drugs are often used in the management of melasma. This work was aimed to investigate the efficacy and safety of herbal drugs on melasma in female patients. METHODS: This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted, and all randomised controlled trials (RCTs) on the use of oral herbal drugs as complementary therapy for melasma in female patients were included. A meta-analysis was conducted according to the guidelines of the Cochrane Collaboration using Review Manager 5.4. RESULTS: Ten eligible trials, with 1015 female melasma patients, were included. All of the included RCTs had some concerns for risk of bias for different reasons, especially for that most of included trials were unblinded. Pooled data suggested phytotherapy plus routine therapy had significantly better efficacy on melasma than routine therapy, in terms of response rate (OR: 4.49, 95% CI: 3.25 to 6.20, p < 0.00001), reduction of skin lesion score (SMD: -0.56, 95% CI: -0.79 to -0.33, p < 0.00001), and improvement of serum E2 levels (SMD: -1.58, 95% CI: -2.62 to -0.55, p 0.003). In addition, there was no significant difference in the incidence of AEs between phytotherapy plus routine therapy and routine therapy (OR: 0.92, 95% CI: 0.53 to 1.58; p 0.76). Overall, herbal drugs used as an adjunct to routine therapy significantly enhanced the efficacy for the treatment of melasma but with a comparable safety profile. CONCLUSION: These findings have implications for recommending herbal drugs as a viable complementary treatment option for melasma.

Langerhans cell histiocytosis misdiagnosed as cow protein allergy: a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a heterogeneous disease with diverse clinical manifestations. Abdominal organ involvement is rare. Early diagnosis and active treatment are needed. The purpose of this article is to enable readers to have a better knowledge of LCH and prevent misdiagnosis. CASE PRESENTATION: A 2-month-old boy had diarrhea, hematochezia, and a rash, and was diagnosed as having a cow milk protein allergy (CMPA). He was given an amino acid-based formula, but there was no sign of improvement in his condition. The patient then had a skin biopsy and was diagnosed as having multisystem Langerhans cell histiocytosis (MS-LCH). The general condition of the child deteriorated after the first two doses of chemotherapy, and the child died. CONCLUSIONS: MS-LCH is a protracted and progressive condition with poor prognosis. Early diagnosis and treatment are essential for survival. If a child has chronic diarrhea and hematochezia in the presence of a characteristic rash, the pediatrician should consider the possibility of this disease to avoid misdiagnosis.

A novel biodegradable injectable chitosan hydrogel for overcoming postoperative trauma and combating multiple tumors.

Wound bacterial infections and tumor recurrence are the main reasons for the poor prognosis after primary tumor resection. Here, we fabricated a novel therapeutic nanocomposite using chitosan (CS) hydrogel combined with black phosphate nanosheets (BPNSs) and in situ grown copper nanoparticles (CuNPs). The obtained hydrogel (CS@BPNSs@CuNPs), possessing a remarkable temperature-sensitive spongy-like state, offered 24.98 % blood clotting index. The released BPNSs@CuNPs could produce reactive oxygen species (ROS) to kill infected invasive bacteria (98.1 %) and inhibit local residual tumor cell regeneration (11.3 %). Moreover, by coupling the photothermal properties of BPNSs, the BPNSs@CuNPs showed 19.6 % penetration rate to cross the blood tumor barrier (BTB) for treating brain tumors. The hydrogel platform was further combined with aPD-L1-based immunotherapy to employ its synergetic therapeutic effect in the prevention of tumors. The in vivo studies showed that biodegradable hydrogel could hold a great potential as a novel strategy for improving postoperative therapy and multi-tumor treatments.

Prevalence of Multidrug-Resistant Tuberculosis in Dalian, China: A Retrospective Study.

PURPOSE: Multidrug-resistant tuberculosis (MDR-TB) is the cause of serious health and economic burdens worldwide. The present study aimed to explore the initial and acquired drug-resistance rates among TB patients from 2012 to 2019 in Dalian, China. The effectiveness of MDR-TB prevention and control strategies were then evaluated. PATIENTS AND METHODS: Drug susceptibility testing (DST) was performed for 6429 diagnosed, culture-positive, Mycobacterium tuberculosis (MTB) strains, including 4661 new cases and 1768 previously treated cases. Descriptive statistics were employed to calculate the frequencies and percentages of TB strains, and the average annual growth rates (AAGRs) for each strain were calculated. The Chi-square test was applied to examine the significance of linear drug-resistance trends over time during the study period. RESULTS: Over the eight-year study period, the percentages of both initial (from 9.01% to 4.82%) and acquired (from 40.85% to 9.09%) MDR-TB cases decreased significantly, AAGRs of 8.55% and 19.32%, respectively. Among new and previously treated TB patients, significant downtrends were observed for the rates of both initial and acquired MDR-TB among young and middle-aged individuals (P < 0.05). Additionally, among both new and previously treated TB patients, the percentages of individuals with drug resistance against isoniazid (INH), rifampicin (RFP), ofloxacin (OFX), and amikacin (AMK) decreased significantly (P < 0.05) from 2012 to 2019 in Dalian, China. CONCLUSION: The initial and acquired multidrug resistance rates exhibited significantly decreasing trends from 2012 to 2019, suggesting that MDR-TB prevalence has been controlled effectively in Dalian, China. The MDR-TB epidemic was reversed in the short term by establishing feasible strategies for detection, diagnosis, treatment, and infection control.

Cut-off Points of Treatment Delay to Predict Poor Outcomes Among New Pulmonary Tuberculosis Cases in Dalian, China: A Cohort Study.

PURPOSE: Despite increasing literature on the association between treatment delay and outcomes, cut-off point (1 month or median) selection in almost all studies for treatment delay is too subjective. This study explored more scientific cut-off points of treatment delay for poor treatment outcomes and death at the clinical level. PATIENTS AND METHODS: A total of 18,100 newly confirmed pulmonary tuberculosis (TB) cases in Dalian, China were used in the final analysis. A 3-knotted restricted cubic spline (RCS) fitted for Cox proportional hazard regression models is used to analyse the effects of cut-off points of treatment delay on incident poor treatment outcomes. To explore the moderating effects of age, gender and diabetes, we added the interaction terms of these moderating variables and treatment delay to Cox proportional hazard regression models. RESULTS: The median time of treatment initiation was 30 days (IQR: 14-59 days). The risk of incident poor treatment outcomes increased when the time was greater than cut-off point 1 (53 days; adjusted HR: 1.26; 95% CI: 1.00-1.60) of treatment delay, and the risk of incident death events increased when the time was greater than cut-off point 2 (103 days; adjusted HR: 1.56; 95% CI: 1.00-2.44) of delay. In addition, treatment delay was associated with an increased risk of incident poor treatment outcomes and death, and older age, male sex, and diabetes may increase the risk of treatment delay for poor outcomes. CONCLUSION: This study is the first to identify scientific cut-off points of treatment delay for poor treatment outcomes and death, and this method of exploration should be popularized. In addition, the knowledge of tuberculosis must be spread to every adult. Moreover, the tuberculosis diagnosis level of community level health workers should be enhanced.

Identification of aberrantly methylated differentially expressed genes in glioblastoma multiforme and their association with patient survival.

Glioblastoma multiforme (GBM) is the most malignant primary tumour type of the central nervous system with limited therapeutic options and poor prognosis, and its pathogenic mechanisms have remained to be fully elucidated. Aberrant DNA methylation is involved in multiple biological processes and may contribute to the occurrence and development of GBM by affecting the expression of certain genes. However, the specific molecular mechanisms remain to be fully elucidated. The present study focused on uncovering differentially expressed genes with altered methylation status in GBM and aimed to discover novel biomarkers for the diagnosis and treatment of GBM. These genes were identified by combined analysis of multiple gene expression and methylation datasets from gene expression omnibus (GSE16011, GSE50161 and GSE 50923) to increase the reliability. In addition, The Cancer Genome Atlas (TCGA) dataset for GBM was used to test the stability of the results. Overall, 251 hypomethylated upregulated genes (Hypo-UGs) and 199 hypermethylated downregulated genes (Hyper-DGs) were identified in the present study. Functional enrichment analysis revealed that the Hypo-UGs are involved in the regulation of immune- and infection-associated signalling, while the Hyper-DGs are involved in the regulation of synaptic transmission. The three hub genes for Hyper-DGs (somatostatin, neuropeptide Y and adenylate cyclase 2) and five hub genes for Hypo-UGs [interleukin-8, matrix metalloproteinase (MMP)9, cyclin-dependent kinase 1, 2'-5'-oligoadenylate synthetase 1, C-X-C motif chemokine ligand 10 and MMP2] were identified by protein-protein interaction network analysis. Among the Hypo-UGs and Hyper-DGs, overexpression of C-type lectin domain containing 5A, epithelial membrane protein 3, solute carrier family 43 member 3, STEAP3 metalloreductase, tumour necrosis factor α-induced protein 6 and apolipoprotein B mRNA editing enzyme catalytic subunit 3G was significantly associated with poor prognosis in the TCGA and GSE16011 datasets (P<0.001). In conclusion, the present study uncovered numerous novel aberrantly methylated genes and pathways associated with GBM. Methylation-based markers, including the hub genes and prognostic genes identified, may potentially serve as markers for the diagnosis of GBM and targets for its treatment.

Aromatization-Driven Cascade [1,5]-Hydride Transfer/Spirocyclization Promoted by Fluorinated Alcohols.

The aromatization-driven redox-neutral cascade [1,5]-hydride transfer/spirocyclization and cascade [1,5]-hydride transfer/hydrolysis from para-quinone methide in HFIP were developed. These protocols enabled the synthesis of azaspirocyclohexadienones and ortho-benzylated anilines in good to high yields under mild conditions, featuring room temperature, additive-free, and good functional group tolerance.

Redox-triggered cascade dearomative cyclizations enabled by hexafluoroisopropanol.

An unprecedented cascade dearomative cyclization through hydrogen-bonding-assisted hydride transfer is realized. The aggregate effect of HFIP enables the rapid buildup of polycyclic amines directly from phenols and o-aminobenzaldehydes via a cascade dearomatization/rearomatization/dearomatization sequence. This unique transformation addressed the drawbacks of hydride transfer-involved redox-neutral reactions.

EGFR confers radioresistance in human oropharyngeal carcinoma by activating endoplasmic reticulum stress signaling PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78.

The activation of epidermal growth factor receptor (EGFR) is associated with radioresistance in malignant tumors. Specifically, radiation can destroy endoplasmic reticulum (ER) homeostasis to induce ER stress (ERS). However, the effect of EGFR-mediated regulation of ERS signaling pathway on radiosensitivity has not yet been reported. The present study showed that silencing EGFR increased radiosensitivity of both radiosensitive and radioresistant oropharyngeal squamous cell carcinoma (OSCC) cells by inhibiting ER stress signaling (PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78). This effect was abolished by pretreatment with EGF, however. In addition, knockdown of EGFR in OSCC cells inhibited DNA double-stand break repair and autophagy while increased radiation-induced apoptosis. Conversely, activating ERS inhibited the aforementioned functions. Furthermore, EGF increased ER stress-independent ERK and AKT signaling upon irradiation of OSCC cells. Immunohistochemical analysis of 80 tissue samples from OSCC patients showed that co-expression of EGFR and PERK was associated with poor prognosis. It thus appears EGFR confers radioresistance in OSCC by activating ER stress signaling. These results suggested that the cooperative effects of radiotherapy and EGFR-targeted inhibitor therapy can be further improved by inhibiting PERK-eIF2α-GRP94 and IRE1α-GRP78 in non-response oropharyngeal carcinoma patients.

Prevalence and risk factors of multi-drug resistant tuberculosis in Dalian, China.

Objectives To investigate the prevalence and risk factors associated with multi-drug resistant tuberculosis (MDR-TB) in Dalian, China. Methods This was a retrospective review of data from patients attending a TB clinic in Dalian, China between 2012 and 2015. Demographic and drug susceptibility data were retrieved from TB treatment cards. Univariate logistic analysis was used to assess the association between risk factors and MDR-TB. Results Among the 3552 patients who were smear positive for Mycobacterium tuberculosis (MTB), 2918 (82.2%) had positive MTB cultures and 1106 (31.1%) had isolates that showed resistance to at least one drug. The overall prevalence of MDR-TB was 10.1% (359/3552; 131/2261 [5.8%] newly diagnosed and 228/1291 [17.7%] previously treated patients). Importantly, 75 extensively drug-resistant TB isolates were detected from 25 newly treated and 50 previously treated patients. In total, 215 (6.1%) patients were infected with a poly-resistant strain of MTB. Previously treated patients and older patients were more likely to develop MDR-TB. Conclusions The study showed a high prevalence of MDR-TB among the study population. History of previous TB treatment and older age were associated with MDR-TB.

Abnormal alterations in the Ca²âº/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg²âº-free solution.

Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence­like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+­free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p­CaMKII; Thr­286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p­CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p­CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co­localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+­free solution.

Application of autochthonous mixed starter for controlled Kedong sufu fermentation in pilot plant tests.

Traditional sufu is fermented by back-slopping and back-slopping has many defects. The objective of this study was to apply autochthonous mixed starter to control Kedong sufu fermentation. Sufu was manufactured using back-slopping (batch A) and autochthonous mixed starter (batch B) with Kocuria kristinae F7, Micrococcus luteus KDF1, and Staphylococcus carnosus KDFR1676. Considering physicochemical properties of sufu, 150-day sufu samples from batch A and 90-day sufu samples from batch B met the standard requirements, respectively. Considering sensory characteristics of sufu, 150-day sufu samples from batch A and 90-day sufu samples from batch B showed no significant differences (P > 0.05). The maturation period of sufu was shortened by 60 d. Profiles of free amino acids and peptides partly revealed the mechanism of typical sensory quality and shorter ripening time of sufu manufactured by autochthonous mixed starter. In final products, content of total biogenic amines was reduced by 48%. Autochthonous mixed starter performed better than back-slopping. Fermentation had a positive influence on the quality, safety, and sensory properties of sufu. The application of autochthonous mixed starter does not change the sensory characteristics of traditional fermented sufu. In addition, it reduces maturation period and improves their homogeneity and safety. It is possible to substitute autochthonous mixed starter for back-slopping in the manufacture of sufu.

Abnormal changes in voltage-gated sodium channels Na(V)1.1, Na(V)1.2, Na(V)1.3, Na(V)1.6 and in calmodulin/calmodulin-dependent protein kinase II, within the brains of spontaneously epileptic rats and tremor rats.

Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. The expressions of different VGSCs subtypes are varied in diverse animal models of epilepsy that may reflect their multiple phenotypes or the complexity of the mechanisms of epilepsy. In a previous study, we reported that NaV1.1 and NaV1.3 were up-regulated in the hippocampus of the spontaneously epileptic rat (SER). In this study, we further analyzed both the expression and distribution of the typical VGSC subtypes NaV1.1, NaV1.2, NaV1.3 and NaV1.6 in the hippocampus and in the cortex of the temporal lobe of two genetic epileptic animal models: the SER and the tremor rat (TRM). The expressions of calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII) were also analyzed with the purpose of assessing the effect of the CaM/CaMKII pathway in these two models of epilepsy. Increased expression of the four VGSC subtypes and CaM, accompanied by a decrease in CaMKII was observed in the hippocampus of both the SERs and the TRM rats. However, the changes observed in the expression of VGSC subtypes and CaM were decreased with an elevated CaMKII in the cortex of their temporal lobes. Double-labeled immunofluorescence data suggested that in SERs and TRM rats, the four subtypes of the VGSC proteins were present throughout the CA1, CA3 and dentate gyrus regions of the hippocampus and temporal lobe cortex and these were co-localized in neurons with CaM. These data represent the first evidence of abnormal changes in expression of four VGSC subtypes (NaV1.1, NaV1.2, NaV1.3 and NaV1.6) and CaM/CaMKII in the hippocampus and temporal lobe cortex of SERs and TRM rats. These changes may be involved in the generation of epileptiform activity and underlie the observed seizure phenotype in these rat models of genetic epilepsy.

The alterations of Ca2+/calmodulin/CaMKII/CaV1.2 signaling in experimental models of Alzheimer's disease and vascular dementia.

The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD). The alterations of Ca(2+)/calmodulin/CaMKII/CaV1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/CaV1.2 by double-labeling immunofluorescence in the hippocampus of APP/PS1 mice and VD gerbils. Additionally, expression of these proteins and intracellular calcium levels were examined in cultured neurons treated with Aß1-42. The expression of CaV1.2 protein was increased in VD gerbils and in cultured neurons but decreased in APP/PS1 mice; the expression of calmodulin protein was increased in APP/PS1 mice and VD gerbils; levels of p-CaMKII, p-CREB and BDNF proteins were decreased in AD and VD models. The number of neurons in which p-CaMKII and CaV1.2 were co-localized, was decreased in the CA1 and CA3 regions in two models. Intracellular calcium was increased in the cultured neurons treated with Aß1-42. Collectively, our results suggest that the alterations in CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF can be reflective of an involvement in the impairment in memory and cognition in AD and VD models.

Ginsenoside Rg(1) inhibits rat left ventricular hypertrophy induced by abdominal aorta coarctation: involvement of calcineurin and mitogen-activated protein kinase signalings.

Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to inhibit proliferation of vascular smooth muscle cells induced by tumor necrosis factor-alpha. This study aims to investigate whether Rg(1) has protective effect on rat left ventricular hypertrophy and to probe its protective mechanisms. The rat left ventricular hypertrophy was induced by abdominal aorta coarctation and Rg(1) (3.75, 7.5 and 15 mg/kg/day) was given the day after surgery for 21 consecutive days. The left ventricular hypertrophy induced by abdominal aorta coarctation was evidenced by histopathology, electromicroscopy, and by determining the elevated left ventricular weight and the expression of atrial natriuretic peptide. Rg(1) significantly ameliorated left ventricular hypertrophy induced by abdominal aorta coarctation in a dose-dependent manner. To examine the mechanism of protection, the expressions of calcineurin, CnA (the catalytic subunit of calcineurin), extracellular signal-regulated kinase-1, and mitogen-activated protein (MAP) kinase phosphatase-1 were determined at the transcript and protein levels. The abdominal aorta coarctation induced increases in calcineurin, CnA, and extracellular signal-regulated kinase-1 expressions were suppressed, but the expression of MAP kinase phosphatase-1 was increased by Rg(1). These results demonstrate that Rg(1) alleviates left ventricular hypertrophy induced by abdominal aorta coarctation, and the protection appears to be due, at least in part, to its inhibitory effects on calcineurin and MAP kinase signaling pathways.