Thermodynamic Study on Hydrogen Reduction of Germanium Tetrachloride to Germanium.

This study elucidates the thermodynamic reaction mechanism of the GeCl4 hydrogen reduction process for Ge preparation. Five independent reactions in the Ge-Cl-H ternary system were identified, utilizing the phase law, mass conservation principles, and thermodynamic data, with H2 as the reducing agent. Additionally, the effects of the temperature, feed ratio, and pressure on the germanium deposition rate during the GeCl4 hydrogen reduction process were investigated, guided by these five reactions. The results indicate that, with fixed temperature and pressure, a higher feed ratio (nH2/nGeCl4) leads to an increased germanium deposition rate. Conversely, with a constant feed ratio, increased pressure results in a lower deposition rate at low temperatures. The optimal operating conditions for germanium preparation via the hydrogen reduction of GeCl4 were determined: the temperature was 450 °C, the feed ratio was 20, the pressure was 0.1 MPa, and the deposition rate of the germanium was 36.12% under this condition.

The Optimization Design of Macrophage Membrane Camouflaging Liposomes for Alleviating Ischemic Stroke Injury through Intranasal Delivery.

Ischemic stroke is associated with a high mortality rate, and effective treatment strategies are currently lacking. In this study, we aimed to develop a novel nano delivery system to treat ischemic stroke via intranasal administration. A three-factor Box-Behnken experimental design was used to optimize the formulation of liposomes co-loaded with Panax notoginseng saponins (PNSs) and Ginsenoside Rg3 (Rg3) (Lip-Rg3/PNS). Macrophage membranes were coated onto the surface of the optimized liposomes to target the ischemic site of the brain. The double-loaded liposomes disguised by macrophage membranes (MM-Lip-Rg3/PNS) were spherical, in a "shell-core" structure, with encapsulation rates of 81.41% (PNS) and 93.81% (Rg3), and showed good stability. In vitro, MM-Lip-Rg3/PNS was taken up by brain endothelial cells via the clathrin-dependent endocytosis and micropinocytosis pathways. Network pharmacology experiments predicted that MM-Lip-Rg3/PNS could regulate multiple signaling pathways and treat ischemic stroke by reducing apoptosis and inflammatory responses. After 14 days of treatment with MM-Lip-Rg3/PNS, the survival rate, weight, and neurological score of middle cerebral artery occlusion (MCAO) rats significantly improved. The hematoxylin and eosin (H&E) and TUNEL staining results showed that MM-Lip-Rg3/PNS can reduce neuronal apoptosis and inflammatory cell infiltration and protect the ischemic brain. In vivo biological experiments have shown that free Rg3, PNS, and MM-Lip-Rg3/PNS can alleviate inflammation and apoptosis, especially MM-Lip-Rg3/PNS, indicating that biomimetic liposomes can improve the therapeutic effects of drugs. Overall, MM-Lip-Rg3/PNS is a potential biomimetic nano targeted formulation for ischemic stroke therapy.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy: Two case reports.

BACKGROUND: The pathological complete response (ypCR) rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol. Immunotherapy has achieved breakthrough progress. CASE SUMMARY: We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0. Detection of mismatch repair protein showed mismatch repair function defect, and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR. Surprisingly, the patients underwent clinical observation after surgery but developed different degrees of metastasis at ~6 mo after surgery. CONCLUSION: PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

O-Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation.

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design of N-protected O-allylhydroxyamines as bifunctional olefins that undergo catalytic asymmetric 1,2-carboamidation with three classes of (hetero)arenes to afford chiral amino alcohols via C-H activation. The C═C bond in O-allylhydroxyamine is activated by the intramolecular electrophilic amidating moiety as well as a migrating directing group. The asymmetric carboamidation reaction pattern depends on the nature of the (hetero)arene reagent. Simple achiral (hetero)arenes reacted to give centrally chiral ß-amino alcohols in excellent enantioselectivity. The employment of axially prochiral or axially racemic heteroarenes afforded amino alcohols with both axial and central chirality in excellent enantio- and diastereoselectivity. In the case of axially racemic heteroarenes, the coupling follows a kinetic resolution pattern with an s-factor of up to >600. A nitrene-based reaction mechanism has been suggested based on experimental studies, and a unique mode of induction of enantio- and diastereoselectivity has been proposed. Applications of the amino alcohol products have been demonstrated.

Mitochondria-targeted fluorescent probe for imaging viscosity in hepatic ischemia-reperfusion injury cell model.

The viscosity of the cell microenvironment is a parameter that affects cell physiological processes. A fluorescent probe X-V was designed to detect the viscosity changes of a hepatic ischemia-reperfusion injury (HIRI) cell model with high selectivity and sensitivity. The fluorescence emission wavelength is 615 nm and the Stokes shift can be up to 125 nm, which can be used not only for intracellular viscosity changes stimulated by different drugs but also for the detection of cell viscosity changes in the HIRI cell model. Probe X-V provides a useful tool to study the relationship between mitochondrial viscosity and related diseases.

Investigation of the "Nose-to-Brain" Pathways in Intranasal HupA Nanoemulsions and Evaluation of Their in vivo Pharmacokinetics and Brain-Targeting Ability.

Purpose: While developing huperzine A (HupA) to explore new approaches to treating Alzheimer's disease (AD), intranasal administration was proposed as an alternative route to deliver drugs into the brain. This study aimed to prepare nanoemulsions (NEs) of HupA to investigate their potential "nose-to-brain" pathways and to evaluate their pharmacokinetic and brain-targeting parameters. Methods: HupA-NE and Lf-HupA-NE that underwent surface modification with lactoferrin (Lf) were characterized to determine various physicochemical properties, such as their size, PDI, zeta potential, pH, and loading efficiency; in addition, transmission electron microscopy and stability assessments were performed. We utilized an aggregation-caused quenching (ACQ) probe to monitor intact NEs in the brains of olfactory nerve transection model and normal rats. Immunohistochemistry, pharmacokinetic and targeting index analyses were performed to investigate the in vivo effects of HupA-NE and Lf-HupA-NE. Results: Based on the live imaging results, HupA-NE and Lf-HupA-NE could be transported into the brain via nerve and blood circulation pathways. Immunohistochemical staining tests demonstrated that the efflux proteins P-gp, MRP1, and BCRP were expressed in brain tissue. NEs can inhibit efflux pumps to improve drug concentrations in the brain. The findings of this study showed that NEs (especially Lf-HupA-NE) had better pharmacokinetic profiles and a better nose-to-brain drug transport efficiency than free HupA. Conclusion: The newly designed formulations might contribute to the transport and accumulation of HupA to achieve therapeutic results. The delivery system may be a promising strategy for the brain-targeted delivery of HupA.

Interleukin 7 inhibit autophagy via P53 regulated AMPK/mTOR signaling pathway in non-small cell lung cancer.

Interleukin 7 (IL-7) has been demonstrated regulating lymphangiogenesis, apoptosis, and proliferation. Whether IL-7 induce or inhibit autophagy in non-small cell lung cancer (NSCLC) are unknown. In this study, Western blot was used to detect cytoplasmic and nuclear protein of p53, total protein of AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Light chain 3 (LC3). Quantitative Real-Time PCR (qRT-PCR) was used to detect p53 mRNA level after treated with IL-7. Then using transmission electron microscopy to observe the morphological change of autophagosome. 123 cases of NSCLC were collected for survival analysis, immunohistochemistry staining and cox regression multivariate analysis. We find that IL-7 induce the p53 translocation from nucleus to cytoplasm, then IL-7 down-regulate phosphorylation of AMPK and up-regulate phosphorylation of mTOR. The expression of AMPK and p53 were associated with IL-7/IL-7R and mTOR expression. Clinically, AMPK and p53 were well correlated with stage and survival of lung cancer patients. IL-7R, mTOR and tumor stage were the strongest predictors of survival. In conclusion, IL-7 inhibit autophagy in NSCLC via P53 regulated AMPK/mTOR signaling pathway. AMPK and p53 are correlated with patients' survival. IL-7R, mTOR and tumor stage are the strongest predictor of survival.

Characterization and Evaluation of the Pro-Coagulant and Immunomodulatory Activities of Polysaccharides from Bletilla striata.

Bletilla striata is widely used for stanching bleeding. In this study, polysaccharides from B. striata (BSP) were extracted by hot water. Four polysaccharides named BSP-1-BSP-4 were fractionated using DEAE-52 cellulose. BSP fractions contained sulfate, and the degrees of substitution of BSP-3 and BSP-4 were 1.59 and 1.70, respectively. Analysis of monosaccharide composition showed that four polysaccharides were mainly composed of mannan and glucose. The in vitro results showed that BSP-1-BSP-4 elicited pro-coagulant capacities by shortening the activating partial thromboplastin time, prothrombin time, and thrombin time and elevating the fibrinogen content. Immunomodulatory activity was evaluated by MTT assay, the pinocytic capacity and NO production. Although BSP fractions did not affect RAW 264.7 cell viability, they, especially BSP-2, enhanced the immunomodulatory activity by increasing the pinocytic capacity and NO production. Overall, BSP may be developed as a potential coagulant with immunomodulatory effects.

Protective Effect of Adalimumab on Diabetic Nephropathy by Regulating TNF-α Signal Pathway.

Background: To evaluate the inhibitory effect of adalimumab on diabetic nephropathy (DN) through animal models. Methods: We carried out the study in Weifang People's Hospital, Weifang 261041, China in December 2020. Streptozotocin was used to induce DN in model animal Sprague-Dawley (SD) rats. The DN animal model was given treatment with adalimumab, and the inhibitory effect of adalimumab on the development process of DN was evaluated by detecting changes in blood glucose and urinary albumin levels. Meanwhile, the content of UN, Cr and CysC of the blood in different experimental groups was tested by weighing the ratio of kidney and performing ELISA to evaluate the protective effect of adalimumab on kidney of DN animal model. In addition, the changes in the transcription and translation levels of tumor necrosis factor alpha (TNF-α) and its downstream regulatory factors MCP-1 and NF-kB in kidney of different experimental groups were detected by fluorescence quantitative PCR and Western blot tests to further reveal the molecular mechanism of adalimumab inhibiting the diabetic nephropathy. Results: adalimumab could significantly downregulate blood glucose and urinary albumin levels (P <0.05). The renal body weight ratio and the contents of UN, Cr and Cysc in blood in the adalimumab group were significantly lower than those in the placebo group (P <0.05). Meanwhile, adalimumab could significantly downregulate the expression of these molecules (P <0.05). Conclusion: adalimumab could exert its therapeutic effect on diabetic nephropathy through its specific targeting TNF-α signaling pathways.

The Distribution and Turnover of Bacterial Communities in the Root Zone of Seven Stipa Species Across an Arid and Semi-arid Steppe.

The bacterial communities of the root-zone soil are capable of regulating vital biogeochemical cycles and the succession of plant growth. Stipa as grassland constructive species is restricted by the difference features of east-west humidity and north-south heat, which shows the population substituting distribution. The distribution, turnover, and potential driving factors and ecological significance of the root-zone bacterial community along broad spatial gradients of Stipa taxa transition remain unclear. This paper investigated seven Stipa species root-zone soils based on high-throughput sequencing combined with the measurements of multiple environmental parameters in arid and semi-arid steppe. The communities of soil bacteria in root zone had considerable turnover, and some regular variations in structure along the Stipa taxa transition are largely determined by climatic factors, vegetation coverage, and pH at a regional scale. Bacterial communities had a clear Stipa population specificity, but they were more strongly affected by the main annual precipitation, which resulted in a biogeographical distribution pattern along precipitation gradient, among which Actinobacteria, Acidobacteria, Proteobacteria, and Chloroflexi were the phyla that were most abundant. During the transformation of Stipa taxa from east to west, the trend of diversity shown by bacterial community in the root zone decreased first, and then increased sharply at S. breviflora, which was followed by continuous decreasing toward northwest afterwards. However, the richness and evenness showed an opposite trend, and α diversity had close association with altitude and pH. There would be specific and different bacterial taxa interactions in different Stipa species, in which S. krylovii had the simplest and most stable interaction network with the strongest resistance to the environment and S. breviflora had most complex and erratic. Moreover, the bacterial community was mainly affected by dispersal limitation at a certain period. These results are conducive to the prediction of sustainable ecosystem services and protection of microbial resources in a semi-arid grassland ecosystem.

Combining the Ultrasound Features of Primary Tumor and Axillary Lymph Nodes Can Reduce False-Negative Rate during the Prediction of High Axillary Node Burden in BI-RADS Category 4 or 5 Breast Cancer Lesions.

The purpose of this study was to determine whether incorporation of the ultrasound (US) features of the primary tumor and axillary lymph node (ALN) could improve the prediction of high axillary nodal burden (HNB) and, thus, avoid unnecessary sentinel lymph node biopsy (SLNB). A total of 347 patients with Breast Imaging Reporting and Data System US category 4 or 5 breast cancer lesions were included. Their pre-operative US features and post-operative pathologic results were collected. The patients were then divided into the following groups based on surgical histology: limited nodal burden (LNB: 0-2 LNs involved) and heavy nodal burden (HNB: ≥3 metastatic LNs). Univariate and multivariate logistic regression analyses were conducted to determine the most valuable variables for HNB prediction. Receiver operating characteristic curves were obtained to assess their values. We found that a non-circumscribed margin, cortical thickness (≥3 mm) and number (≥3) of suspicious ALNs are indicators for HNB prediction. The false-negative rate (FNR) in model 1 (cortical thickness + number of suspicious ALNs) was 15.5% versus 3.4% in model 2 (non-circumscribed margin + cortical thickness + number of suspicious ALNs). Our results indicate that combining the US features of the primary tumor and ALNs can reduce the FNR during HNB prediction.

The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route.

BACKGROUND: Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer's disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems. PURPOSE: The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration. METHODS: The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency. RESULTS: Optimized HupA-NE had a particle size of 15.24±0.67 nm, polydispersity index (PDI) of 0.128±0.025, and zeta potential of -4.48±0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2±0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE. CONCLUSION: Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.

Heterostructured SnO2-SnS2@C Embedded in Nitrogen-Doped Graphene as a Robust Anode Material for Lithium-Ion Batteries.

Tin-based anode materials with high capacity attract wide attention of researchers and become a strong competitor for the next generation of lithium-ion battery anode materials. However, the poor electrical conductivity and severe volume expansion retard the commercialization of tin-based anode materials. Here, SnO2-SnS2@C nanoparticles with heterostructure embedded in a carbon matrix of nitrogen-doped graphene (SnO2-SnS2@C/NG) is ingeniously designed in this work. The composite was synthesized by a two-step method. Firstly, the SnO2@C/rGO with a nano-layer structure was synthesized by hydrothermal method as the precursor, and then the SnO2-SnS2@C/NG composite was obtained by further vulcanizing the above precursor. It should be noted that a carbon matrix with nitrogen-doped graphene can inhibit the volume expansion of SnO2-SnS2 nanoparticles and promote the transport of lithium ions during continuous cycling. Benefiting from the synergistic effect between nanoparticles and carbon matrix with nitrogen-doped graphene, the heterostructured SnO2-SnS2@C/NG further fundamentally confer improved structural stability and reaction kinetics for lithium storage. As expected, the SnO2-SnS2@C/NG composite exhibited high reversible capacity (1201.2 mA h g-1 at the current rate of 0.1 A g-1), superior rate capability and exceptional long-life stability (944.3 mAh g-1 after 950 cycles at the current rate of 1.0 A g-1). The results demonstrate that the SnO2-SnS2@C/NG composite is a highly competitive anode material for LIBs.

Pharmacokinetics and liver uptake of three Schisandra lignans in rats after oral administration of liposome encapsulating ß-cyclodextrin inclusion compound of Schisandra extract.

Schisandra chinensis fructus (SCF) is widely used traditional Chinese medicine, which possesses hepato-protective potential. Schisandrin (SD), schisantherin (ST), and γ-schizandrin (SZ) are the major bioactive lignans. The main problem associated with the major bioactive lignans oral administration is low oral bioavailability due to the lignans' poor aqueous solubility and taste. The aim of the present research work was to develop liposome (SCL) encapsulated ß-cyclodextrin (ß-CD) inclusion complex loaded with SCF extract (SCF-E). The SD, ST, and SZ were selected as effective candidates to perform comparisons of liver targeting among the solution (SES), ß-cyclodextrin inclusion compound (SCF-E-ß-CD), liposome (SEL), and SCL of SCF-E to characterize the pharmacokinetic behaviors and liver targeting in rats. The ß-CD inclusion complex (SCF-E-ß-CD) was used to improve the solubility. The concentrations were determined using high-performance liquid chromatography (HPLC) and analyzed by DAS3.0. The pharmacokinetic results indicate that the plasma concentration-time courses were fitted well to the one-compartment model with the first weighing factor. The half-life period (t1/2) and area under the concentration-time curve (AUC) of the three components in SCL were the largest. The SCL exhibit a relatively high liver targeting effect. The results would be helpful for guiding the clinical application of this herbal medicine.

The synergistic effect of 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside combined with Adriamycin on MCF-7 breast cancer cells.

OBJECTIVE: Breast cancer has been reported to be a serious disease and a threat to women's health. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside (THSG) is a bioactive natural compound originating from Polygonum multiflorum Thunb., which has been shown to possess anti-inflammatory and antitumor properties. Adriamycin (ADM) is a chemotherapy agent used in tumor therapy that is limited by its side effects. However, little is known about the synergistic effect of THSG combined with ADM on breast cancer. This study seeks to investigate the effects of the combination of THSG plus ADM on MCF-7 breast cancer cells and to test the mechanisms involved. MATERIALS AND METHODS: MTT assay was detected to determine cell viability. Furthermore, cell apoptosis was tested by flow cytometry and TUNEL assay. In addition, protein expression was measured by Western blot analysis. RESULTS: The individual treatment of THSG and ADM induced cell injury. Moreover, cotreatment further increased it, which the effect may be associated with the elevation of the apoptotic-related protein expression such as Bax/Bcl-2 and cleaved caspase-3/caspase-3. Lastly, our results also show the reduction of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt protein expression in the individual or synergistic treatment. CONCLUSION: Taken together, cotreatment of THSG and ADM may exert a synergistic reduction of cell injury via the inhibition of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt pathway. Thus, THSG might possess potent anti-breast cancer effect with ADM.

Reduced Graphene Oxide Decorated Na3V2(PO4)3 Microspheres as Cathode Material With Advanced Sodium Storage Performance.

Reduced graphene oxide (rGO) sheet decorated Na3V2(PO4)3 (NVP) microspheres were successfully synthesized by spray-drying method. The NVP microspheres were embedded by rGO sheets, and the surface of the particles were coated by rGO sheets and amorphous carbon. Thus, the carbon conductive network consisted of rGO sheets and amorphous carbon generated in the cathode material. NVP microspheres decorated with different content of rGO (about 0, 4, 8, and 12 wt%) were investigated in this study. The electrochemical performance of NVP exhibited a significant enhancement after rGO introduction. The electrode containing about 8 wt% rGO (NVP/G8) showed the best rate and cycle performance. NVP/G8 electrode exhibited the discharge capacity of 64.0 mAh g-1 at 70°C, and achieved high capacity retention of 95.5% after cycling at 10°C for 100 cycles. The polarization of the electrode was inhibited by the introduction of rGO sheets. Meanwhile, compared with the pristine NVP electrode, NVP/G8 electrode exhibited small resistance and high diffusion coefficient of sodium ions.

In-situ Grown SnS2 Nanosheets on rGO as an Advanced Anode Material for Lithium and Sodium Ion Batteries.

SnS2 nanosheets/reduced graphene oxide (rGO) composite was prepared by reflux condensation and hydrothermal methods. In this composite, SnS2 nanosheets in-situ grew on the surface of rGO nanosheets. The SnS2/rGO composite as anode material was investigated both in lithium ion battery (LIB) and sodium ion battery (SIB) systems. The capacity of SnS2/rGO electrode in LIB achieved 514 mAh g-1 at 1.2 A g-1 after 300 cycles. Moreover, the SnS2/rGO electrode in SIB delivered a discharge capacity of 645 mAh g-1 at 0.05 A g-1; after 100 cycles at 0.25 A g-1, the capacity retention still keep 81.2% relative to the capacity of the 6th cycle. Due to the introduction of rGO in the composite, the charge-transfer resistance became much smaller. Compared with SnS2/C electrode, SnS2/rGO electrode had higher discharge capacity and much better cycling performance.

Black Anatase Titania with Ultrafast Sodium-Storage Performances Stimulated by Oxygen Vacancies.

Nanostructured black anatase titania with oxygen vacancies (OVs) is efficiently obtained and employed as an anode in sodium-ion batteries (SIBs) for the first time. The incorporation of OVs into TiO2 is demonstrated to render considerably enhanced-rate performances, higher initial capacities, and an accelerated electrochemical activation process during cycling, derived from the boosted intrinsic electric conductivity and improved kinetics of Na uptake. Bestowed with the integrated merits of OVs and shortened Na ion diffusion length in the nanostructure, black titania delivers a reversible specific capacity of 207.6 mAh g(-1) at 0.2 C, retains 99.1% over 500 cycles at 1 C stably, and still maintains 91.2 mAh g(-1) even at the high rate of 20 C. Density functional theory (DFT) calculations suggest that the lower sodiation energy barrier of anatase with OVs enables a more favorable Na intercalation into black anatase. Thus, it is of great significance to introduce OVs into TiO2 to stimulate ultrafast and durable sodium-storage properties, which also offers a potential strategy to project more superior electrodes, utilizing internal defects.