Berberine chloride suppresses pancreatic adenocarcinoma proliferation and growth by targeting inflammation-related genes: an in silico analysis with in vitro and vivo validation.

PURPOSE: Targeting inflammatory crosstalk between tumors and their microenvironment has emerged as a crucial method for suppressing pancreatic adenocarcinoma (PAAD) progression. Berberine (BBR) is a natural pentacyclic isoquinoline alkaloid known for its anti-inflammatory and antitumor pharmacological effects; however, the mechanism underlying PAAD suppression remains unclear. We aim to investigate the effects of BBR on PAAD progression and their underlying mechanisms. METHODS: The prognostic value of inflammation-related genes in PAAD was assessed using bioinformatics analyses, then the pharmacological effects and potential mechanisms of BBR on PAAD will be investigated in silico, in vitro, and in vivo. RESULTS: Fifty-eight prognostic inflammation-related genes were identified in PAAD, which were shown to have good sensitivity and specificity using a novel inflammation-related gene risk-prognosis prediction model. Among these, four candidate genes (CAPS3, PTGS2, ICAM1, and CXCR4) were predicted as targets of BBR in PAAD in silico. Molecular docking simulations showed that the four key targets docked well with BBR. Further BBR treatment suppressed cell proliferation, colony formation, and induced cell cycle arrest in vitro. Moreover, BBR exhibited a significant tumor-suppressive effect in murine subcutaneous xenografts without macroscopic hepatic and renal toxicities. In addition, BBR downregulated CAPS3, PTGS2, ICAM1, and CXCR4 protein expression. CONCLUSION: This study not only elucidated the prognostic value of inflammation-related genes in PAAD but also demonstrated the potential of BBR to inhibit PAAD by targeting these genes.

Role and molecular mechanism of APOBEC3B in the development and progression of gastric cancer.

Gastric cancer is a common malignant tumor with a high mortality rate. Abnormal APOBEC3B (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3B) expression increases tumor susceptibility. However, the exact molecular mechanism of APOBEC3B expression in the development of gastric cancer is still unknown. We investigated the effect of APOBEC3B on the malignant biological behavior of gastric cancer cells and discussed the role of APOBEC3B in the development and progression of gastric cancer. APOBEC3B protein levels were measured in 161 gastric cancer samples using western blotting and immunohistochemistry. Both in vitro and in vivo assays were performed, and molecules were analyzed using bioinformatics analysis and western blotting. APOBEC3B was overexpressed in gastric cancer. Moreover, APOBEC3B significantly enhanced cell proliferation in vitro and tumorigenicity in vivo. Regarding the underlying mechanism, APOBEC3B promoted the proliferation of gastric cancer cells by upregulating P53, MCM2 (minichromosome maintenance protein 2), and cyclin D1. Our results suggest that APOBEC3B is involved in cancer progression, providing a new theoretical basis for the prevention and treatment of gastric cancer.

Dry-Processable Polymer Electrolytes for Solid Manufactured Batteries.

Designing a solid-state electrolyte that satisfies the operating requirements of solid-state batteries is key to solid-state battery applications. The consensus is that solid-state electrolytes need to allow fast ion transport, while providing better interfacial compatibility and mechanical tolerance. Herein, a simple but effective strategy is proposed, combining hard and soft component polymer systems, to exploit a solid polymer electrolyte (SPE) with a 3D network via an in situ graft polymerization. The 3D structure is constructed by a hard cellulose nanocrystal (CNC) as the skeleton and a soft polyacrylonitrile (PAN) as the filler through a dry-processing method. The reported systems have several advantages, including ease of processing, only requiring using an exceedingly small amount of solvent, light weight (ρ = 1.2 g cm-3), excellent mechanical stability (tensile strength of 9.5 MPa), and high ionic conductivity (3.9 × 10-4 S cm-1, 18 °C) and migration number (tLi+ = 0.8). In particular, the high conductivity is enabled: the efficient Li+ transportation path constructed between CNC-PAN powders and abundant sulfonate radicals and hydroxyl groups on the CNC surface acts as the bridge of Li+ transition. When the CNCs are grafted onto the PAN polymer, the dipole-dipole interaction between the nitrile groups of the PAN and the hydroxyl groups of the CNCs can help to improve the mechanical stability and ionic conductivity of the SPE. Moreover, a tightly formed interface between SPE and LiFePO4 (LFP)/carbon black/SPE cathode can be achieved in an assembled solid-state battery by hot pressing, thus further enhancing the battery's performance.

LSR targets YAP to modulate intestinal Paneth cell differentiation.

Lipolysis-stimulated lipoprotein receptor (LSR) is a multi-functional protein that is best known for its roles in assembly of epithelial tricellular tight junctions and hepatic clearance of lipoproteins. Here, we investigated whether LSR contributes to intestinal epithelium homeostasis and pathogenesis of intestinal disease. By using multiple conditional deletion mouse models and ex vivo cultured organoids, we find that LSR elimination in intestinal stem cells results in the disappearance of Paneth cells without affecting the differentiation of other cell lineages. Mechanistic studies reveal that LSR deficiency increases abundance of YAP by modulating its phosphorylation and proteasomal degradation. Using gain- and loss-of-function studies, we show that LSR protects against necrotizing enterocolitis through enhancement of Paneth cell differentiation in small-intestinal epithelium. Thus, this study identifies LSR as an upstream negative regulator of YAP activity, an essential factor for Paneth cell differentiation, and a potential therapeutic target for necrotizing enterocolitis.

Solvation and Interfacial Engineering Enable -40 °C Operation of Graphite/NCM Batteries at Energy Density over 270 Wh kg-1.

Li-ion batteries (LIBs) that can operate under low temperature (LT) conditions are essential for applications in orbital missions, subsea areas, and electric vehicles. Unfortunately, severe capacity loss is witnessed due to tremendous kinetic barriers that emerge at LT. Herein, to surmount such kinetic limitations, a low dielectric environment is tamed throughout the bulk electrolyte, which efficaciously brought the Li+ desolvation energy down to 30.76 kJ mol-1 . At the meantime, the adoption of sodium cations (Na+ ) is proposed as a hetero-cation additive, and a Li-Na hybrid and fluoride-rich interphase is further identified via preferential reduction of Na+ -(solvent/anion) clusters, which is found to efficiently facilitate Li+ migration through the LiF/NaF grain boundaries. Based on a N/P ratio of 1.1, the graphite/LiNi0.5 Co0.2 Mn0.3 O2 (NCM) full cell (cathode loading of ≈18.5 mg cm-2 ) delivers a capacity as high as 125.1 mAh g-1 under -20 °C with prolonged cycling to 100 cycles. Finally, a 270 Wh kg-1 graphite/NCM pouch cell is assembled, which affords a discharge capacity of 108.7 mAh g-1 under -40 °C during the initial cycles. With an eye to both fundamental and practical aspects, this work will propel additional advancements and allow LIBs to fill more roles under extreme operation temperatures than ever before.

Simultaneous telemetry of temperature and vibration by laser dispersion spectroscopy.

In many industrial applications, temperature and mechanical vibration are closely coupled but measured separately. A novel, to the best of our knowledge, method for simultaneous telemetry of temperature and vibration parameters was proposed in this work from laser dispersion spectroscopy profiles at two different central wavelengths. The temperature was extracted from the peak-to-peak ratio of these two absorption spectra. The vibration amplitude as well as its frequency were derived from the time-varying baselines of the two spectra. A telemetry sensor was designed and evaluated on a thermal vibration coupled experiment platform. The extracted temperatures agree well with the readings of a reference thermocouple, and the signal-to-noise ratio is at least 18 dB higher than those by classical direct laser absorption spectroscopy (DLAS). The extracted vibration frequencies are the same as the outputs of a commercial laser Doppler vibrometer (LDV), and the sensitivity of the extracted vibration amplitudes is 3.64 micrometers, in terms of the Allan variance.

Resveratrol Downregulates miR-155-5p to Block the Malignant Behavior of Gastric Cancer Cells.

Studies have shown that resveratrol (Res) exerts significant antiproliferative effects in cancer, and regulating the expression of microRNAs (miRNAs) is one the underlying mechanisms of these effects. Overexpression of miR-155-5p leads to oncogenesis. However, it is unclear whether Res exerts antitumor effects by regulating the expression of miR-155-5p, and its specific mechanism in gastric cancer remains unknown. In this study, qRT-PCR was performed to assess the expression of miR-155-5p in gastric cells and clinical tissues, and the MTT assay, plate clone formation test, cell scratch test, Transwell assay, and flow cytometry were performed to investigate the functions of Res on the growth of gastric cancer cells after treatment with miR-155-5p. Western blot analysis was performed to detect the expression of claudin 1, c-Myc, cyclin D1, Bcl-2, and caspase-3 proteins in gastric cancer cell lines after treatment with miR-155-5p and Res. We found that miR-155-5p was overexpressed in gastric cancer cells and clinical tissues, while Res inhibited gastric cancer cell growth by regulating miR-155-5p expression. The results of MTT assay, plate clone formation test, cell scratch test, Transwell test, and flow cytometry showed that miR-155-5p promoted the proliferation, invasion, and metastasis of gastric cancer cell lines and inhibited apoptosis, while Res addition inhibited this effect (P < 0.05). When miR-155-5p was overexpressed, the expressions of claudin 1, c-Myc, cyclin D1, and Bcl-2 were upregulated and that of caspase-3 was downregulated. Collectively, these results suggest that miR-155-5p may be a therapeutic target in gastric cancer, and Res may be a potential therapeutic agent based on its regulation of miR-155-5p.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor.

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Epidemic status of imported malaria before and after malaria elimination in Jiaozuo City of Henan Province / 中国血吸虫病防治杂志

Objective To analyze and compare the epidemiological characteristics of imported malaria in Jiaozuo City before and after malaria elimination, so as to provide insights into the malaria surveillance during the post-elimination stage and prevention of re-establishment of imported malaria. Methods Data pertaining to the epidemic situation and individual investigation of malaria in Jiaozuo City before (from 2010 to 2016) and after malaria elimination (from 2017 to November, 2020) were captured from the National Notifiable Disease Reporting System and the Information System for Parasitic Diseases Control and Prevention of Chinese Center for Disease Control and Prevention and were analyzed statistically. Results A total of 74 imported malaria cases were reported in Jiaozuo City from 2010 to 2021. Imported cases were predominantly Plasmodium falciparum malaria cases in Jiaozuo City before and after malaria elimination, and there was no significant difference in the proportion of malaria parasite species (χ2 = 0.234, P > 0.05). The imported malaria cases was predominantly reported in Wuzhi County, and was identified in overseas male farmers and businessmen at ages of 20 to 59 years, while the greatest number of imported malaria cases was reported in June and December before and after malaria elimination. The imported malaria cases predominantly acquired malaria parasite infections in sub-Saharan African countries; however, the proportion of imported malaria cases returning from Southeast Asian counties increased after malaria elimination than before malaria elimination (χ2 = 5.989, P < 0.05). The longest duration from onset to definitive diagnosis of malaria reduced from 27 days before malaria elimination to 18 days after malaria elimination, and the median duration reduced from 3 days to 2 days, while the proportion of definitive diagnosis of malaria increased from 60.47% before malaria elimination to 83.87% after malaria elimination (χ2 = 4.724, P < 0.05). In addition, the proportion of malaria cases definitively diagnosed and reported by medical institutions increased after malaria elimination than before malaria elimination (χ2 = 5.406, P < 0.05). Conclusions The imported malaria patients were predominantly P. falciparum malaria cases in Jiaozuo City during 2010 to 2021, and the patient’s medical care-seeking awareness and medical staff’s diagnosis and treatment ability have improved after malaria elimination. It is necessary to strengthen and improve malaria surveillance and response system and prevent the re-establishment of overseas imported malaria.

The Legislative Approach and System Improvement of China's Compulsory Licensing for Drug Patents.

Compulsory licensing for drug patents is of great significance to ensure the accessibility of drugs. Although the development of China's compulsory licensing system for drug patents has been gradually improved, there are still problems. For example, the scope of the object is not realistic, the setting of the initiating subject is unreasonable, the reasons for issuance are not clear, the duration and scope of the license are not refined, and the provisions on the exploitation fee are missing. Consequently, in order to improve China's compulsory licensing system for drug patents, it is necessary to expand reasonably the scope of the object, remove the restrictions on the initiating subject, adjust the initiating rights of different subjects, determine the duration and scope of the license and the applicability of the hearing on a case-by-case basis, and determine a reasonable exploitation fee by taking into account the national income, patent cost, market share and other factors, in consideration of the flexibly international norms and the actual situation in China.

Electrolyte Design Enabling a High-Safety and High-Performance Si Anode with a Tailored Electrode-Electrolyte Interphase.

Silicon (Si) anodes are advantageous for application in lithium-ion batteries in terms of their high theoretical capacity (4200 mAh g-1 ), appropriate operating voltage (<0.4 V vs Li/Li+ ), and earth-abundancy. Nevertheless, a large volume change of Si particles emerges with cycling, triggering unceasing breakage/re-formation of the solid-electrolyte interphase (SEI) and thereby the fast capacity degradation in traditional carbonate-based electrolytes. Herein, it is demonstrated that superior cyclability of Si anode is achievable using a nonflammable ether-based electrolyte with fluoroethylene carbonate and lithium oxalyldifluoroborate dual additives. By forming a high-modulus SEI rich in fluoride (F) and boron (B) species, a high initial Coulombic efficiency of 90.2% is attained in Si/Li cells, accompanied with a low capacity-fading rate of only 0.0615% per cycle (discharge capacity of 2041.9 mAh g-1 after 200 cycles). Full cells pairing the unmodified Si anode with commercial LiFePO4 (≈13.92 mg cm-2 ) and LiNi0.5 Mn0.3 Co0.2 O2 (≈17.9 mg cm-2 ) cathodes further show extended service life to 150 and 60 cycles, respectively, demonstrating the superior cathode-compatibility realized with a thin and F, B-rich cathode electrolyte interface. This work offers an easily scalable approach in developing high-performance Si-based batteries through Si/electrolyte interphase regulation.

HELLS serves as a poor prognostic biomarker and its downregulation reserves the malignant phenotype in pancreatic cancer.

BACKGROUND: SMARCAs, belonged to SWI/SNF2 subfamilies, are critical to cellular processes due to their modulation of chromatin remodeling processes. Although SMARCAs are implicated in the tumor progression of various cancer types, our understanding of how those members affect pancreatic carcinogenesis is quite limited and improving this requires bioinformatics analysis and biology approaches. METHODS: To address this issue, we investigated the transcriptional and survival data of SMARCAs in patients with pancreatic cancer using ONCOMINE, GEPIA, Human Protein Atlas, and Kaplan-Meier plotter. We further verified the effect of significant biomarker on pancreatic cancer in vitro through functional experiment. RESULTS: The Kaplan-Meier curve and log-rank test analyses showed a positive correlation between SMARCA1/2/3/SMARCAD1 and patients' overall survival (OS). On the other hand, mRNA expression of SMARCA6 (also known as HELLS) showed a negative correlation with OS. Meanwhile, no significant correlation was found between SMARCA4/5/SMARCAL1 and tumor stages and OS. The knockdown of HELLS impaired the colony formation ability, and inhibited pancreatic cancer cell proliferation by arresting cells at S phase. CONCLUSIONS: Data mining analysis and cell function research demonstrated that HELLS played oncogenic roles in the development and progression of pancreatic cancer, and serve as a poor prognostic biomarker for pancreatic cancer. Our work laid a foundation for further clinical applications of HELLS in pancreatic cancer.

In Situ Transformed Solid Electrolyte Interphase by Implanting a 4-Vinylbenzoic Acid Nanolayer on the Natural Graphite Surface.

A solid electrolyte interphase (SEI) layer on a graphite anode plays a crucial role in deciding electrochemical properties of the electrode including the first Coulombic efficiency, rate capability, operating temperature, and long-term cycling stability. However, the ultrathin functional SEI layer is always naturally grown via electrolyte reduction decomposition reactions. Herein, we report a new strategy of in situ transformed solid electrolyte interphase of high stability by implanting a 4-vinylbenzoic acid (4-VBA) nanolayer on a mildly oxidized graphite surface. A 4-VBA layer of 40 nm contributes to the transformation of a robust and stable SEI layer, which not only significantly enhances the overall electrochemical performances of the natural graphite electrode but also greatly prolongs the cycle life of the full cell with the LiNi0.6Co0.2Mn0.2O2 cathode. The effectively suppressed surface evolution aroused from the stable organic SEI transformed from the implanted 4-VBA nanolayer explains the enhanced electrochemical properties.

The association between prostate weight and positive surgical margins in prostate cancer: A meta-analysis.

There have been some conflicting claims whether larger prostate weight (PW) reduces the risk of positive surgical margins (PSMs). This study aims to examine the associations between PW and PSMs. PubMed, Web of Science and Cochrane library were systematically retrieved. Relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were synthesised utilising random-effect models. Ultimately, 22 cohort studies met criteria were enrolled in this meta-analysis, of which 18 studies reporting the RR of the highest VS lowest category of PW yielded the combined RR of PSMs of 0.61 (95% CI 0.50-0.74). Subgroup analysis showed that geographic region and surgical modalities were considered as potential confounders of influence of PW on PSMs. The nonlinear dose-response relationship demonstrated that PSM risk decreased by 1% (RR = 0.99, 95% CI, 0.98-0.99) for every one gram increment in PW. This study suggests PW has a negative association with risk of PSMs, and having a appropriate PW is very important.

Random vibration-driven continuous-wave CRDS system for calibration-free gas concentration measurement.

Random vibrations were employed to pick up each monochromatic component in a continuous-wave cavity ringdown spectroscopy (CRDS) system using a bichromatic laser source. Light frequencies were selected within flat portions of an absorption profile to suppress the jitter in laser frequency during measurements. An interference effect caused by cavity length variations was suppressed by optimizing the initial fit point for each ringdown transient. The difference in exponential decay rates of two frequencies determined the gas mole fraction, and no calibration of empty cavity losses was necessary. Experiments on varying humidity were conducted, and the results agreed with the readings of a commercial hygrometer.

Corrigendum: ß-Sitosterol and Gemcitabine Exhibit Synergistic Anti-Pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3ß Signaling.

[This corrects the article DOI: 10.3389/fphar.2018.01525.].

Boosting the Reversibility of Sodium Metal Anode via Heteroatom-Doped Hollow Carbon Fibers.

Sodium (Na) metal anodes stand out with their remarkable capacity and natural abundance. However, the dendritic Na growth, infinite dimensional changes, and low Coulombic efficiency (CE) present key bottlenecks plaguing practical applications. Here, heteroatom-doped (nitrogen, sulfur) hollow carbon fibers (D-HCF) are rationally synthesized as a nucleation-assisting host to enable a highly reversible Na metal. The "sodiophilic" functional groups introduced by the heteroatom-doping and large surface area (≈1052 m2 g-1 ) synchronously contribute to a homogenous plating morphology with dissipated local current density. High "sodiophilicity" of the D-HCF is confirmed by first-principle calculations and experimental results, where strong adsorption energy of -3.52 eV with low Na+ nucleation overpotential of 3.2 mV at 0.2 mA cm-2 is realized. As such, highly reversible plating/stripping is achieved at 1.0 mA cm-2 with average CE approximating 99.52% over 600 cycles. The as-assembled Na@D-HCF symmetric cells exhibit a prolonged lifetime for 1000 h. A full-cell paired with Na3 V2 (PO4 )3 cathode further demonstrates stable electrochemical behavior for 200 cycles at 1 C along with excellent rate performance (102 mAh g-1 at 5 C). The results clearly show the effectiveness of the D-HCF in manipulating Na+ deposition and thus the significance of nucleation control in realizing dendrite-free metal anodes.

Adaptive Selection of Truncation Radius in Calderon's Method for Direct Image Reconstruction in Electrical Capacitance Tomography.

Calderon's method has been successfully used for the direct image reconstruction in electrical capacitance tomography. In the method, the truncation radius adopted in numerical integral greatly influences the reconstruction results. In the past, the truncation radius is selected as a constant empirically according to the permittivity distribution pattern and noise level. In this paper, the influence of the truncation radius in Calderon's method on the reconstruction results was first analyzed by numerical simulation. Then, a strategy for adaptive selection of the truncation radius was proposed. The amplitude information of the elements in the scattering transform matrix computed from the Dirichlet-to-Neumann (DN) map was used to determine the range for the truncation radius selection, and the phase information was further used to select a proper truncation radius value within this selection range. Finally, experiments were carried out to verify the strategy. Experimental results showed that small relative image error and good visual effect could be obtained by using the truncation radius selected by the proposed strategy.

𝛍m-resolution thickness distribution measurement of transparent glass films by using a multi-wavelength phase-shift extraction method in the large lateral shearing interferometer.

In this paper, a precise phase-shift extraction method was introduced for the first time to measure the thickness distribution of transparent glass films. A spatial light modulator modulated the phases of the incident laser in a large lateral shearing interferometer. The phase shifting caused by the thickness of the films can be extracted ranging from 0 to 2π, in a recursive way suitable for real-time implementation. Incident lasers with different wavelengths were utilized to measure the spatial distribution of the thickness of the films, and they can be larger than one wavelength of the incident light. Both artificial and experimental results have verified that the resolution of the thickness measurement reaches up to 1 𝛍m.