Comprehensive Systematic Review of Poly-L-lactic Acid in Facial Clinical Application.

OBJECTIVES: With the increasing global clinical application of regenerative injection materials, there is a growing recognition of the crucial role played by poly-L-lactic acid (PLLA). The aim of this study is to conduct a systematic review on the therapeutic efficacy and safety of PLLA in clinical applications for facial treatments. METHODS: We conducted a search of the PubMed, EMBASE, Web of Science, and Wanfang databases, followed by screening of the retrieved articles based on predefined inclusion and exclusion criteria. We then performed an analysis on the final set of included articles that met our inclusion criteria. Within these included articles, quality assessment for randomized controlled trials (RCTs) was carried out using the Jadad scale, while non-randomized controlled trials (non-RCTs) were evaluated using the MINORS scale. RESULTS: Our search of above database, using the relevant search terms, yielded a total of 1300 PLLA-related articles. After applying the inclusion and exclusion criteria, 1280 articles were excluded. Only 20 articles, 16 in English and 4 in Chinese, were included in our final analysis, among them 16 NRCTs and 4 RCTs. According to the different clinical evaluation standards, the treatment of PLLA has achieved good outcomes. Most PLLA injection-related adverse events are mild and self-limited, without any additional treatment requirement. CONCLUSION: PLLA is a reasonably safe and effective facial injection material that can be applied in different facial injection areas and depth using various reconstitute and injection methods. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Adsorption properties of Pb(II) and Cd(II) in acid mine drainage by oyster shell loaded lignite composite in different morphologies.

A new idea to alleviate environmental pollution is the development of low-cost adsorbents using natural minerals and fishery wastes to treat high concentrations of heavy metal pollutants in acid mine drainage (AMD). Adsorbent morphology, adsorptive and regenerative capacity, and application potential are limiting factors for their large-scale use. Oyster shells capable of releasing alkalinity were loaded on the surface of lignite to develop two composite adsorbents with different morphologies (powdery and globular) for the treatment of AMD containing Pb(II) and Cd(II). The results show that the ability of the adsorbent to treat AMD is closely related to its morphologies. The pseudo-second-order kinetic model and the Langmuir model are suitable to describe the adsorption process of OS-M(P), and the maximum adsorption saturation capacities of Pb(II) and Cd(II) are 332.6219 mg/g and 318.9854 mg/g, respectively. The pseudo-second-order kinetic model and the Freundlich model are suitable to describe the adsorption process of OS-M(G). A synergistic result of electrostatic adsorption, neutralization precipitation, ion exchange and complex reaction is achieved in the removal of Pb(II) and Cd(II) by two morphologies of adsorbents. The regeneration times (5 times) and recovery rate (75.75%) of OS-M(G) are higher than those of OS-M(P) (3 times) and recovery rate (20%). The ability of OS-M(G) to treat actual AMD wastewater is still better than that of OS-M(P). OS-M(G) can be used as a promising environmentally friendly adsorbent for the long-term remediation of AMD. This study provides a comprehensive picture of resource management and reuse opportunities for natural mineral and fishery wastes.

DEAD-Box Helicase 17 circRNA (circDDX17) Reduces Sorafenib Resistance and Tumorigenesis in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy. Despite significant progress in HCC treatment, resistance to chemotherapy and tumor metastasis are the main reasons for the unsatisfactory prognosis of HCC. Circular RNAs (circRNAs) have been extensively documented to play a role in the development of various types of cancer. AIMS: Here, we investigated the role of DEAD-box helicase 17 circRNA (circDDX17) in HCC and its underlying molecular mechanisms. METHODS: Our research employed various techniques including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8), flow cytometry, dual luciferase reporter assay, RNA immunoprecipitation (RIP), and western blot analysis. Additionally, we conducted a tumor xenograft assay to investigate the in vivo function of circDDX17. RESULTS: Firstly, the expression of circDDX17 was downregulated in HCC tissues and cells. Through functional experiments, it was observed that the overexpression of circDDX17 enhanced the sensitivity of sorafenib, promoted apoptosis, and inhibited the process of epithelial-mesenchymal transition (EMT) in vitro. Additionally, in vivo studies revealed that circDDX17 reduced tumor growth and increased sorafenib sensitivity. Mechanically, circDDX17 competitively combined miR-21-5p to suppress PTEN expression and activate the PI3K/AKT pathway. Furthermore, our rescue assays demonstrated that circDDX17 act as a tumor suppressor by blocking sorafenib resistance and tumorigenesis, while the inhibitory effect caused by circDDX17 upregulation was neutralized when miR-21-5p was overexpressed, PTEN was silenced, or the PI3K/AKT pathway was activated. CONCLUSION: Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.

Indoxyl sulphate-TNFα axis mediates uremic encephalopathy in rodent acute kidney injury.

Acute kidney injury (AKI) is often accompanied by uremic encephalopathy resulting from accumulation of uremic toxins in brain possibly due to impaired blood-brain barrier (BBB) function. Anionic uremic toxins are substrates or inhibitors of organic anionic transporters (OATs). In this study we investigated the CNS behaviors and expression/function of BBB OAT3 in AKI rats and mice, which received intraperitoneal injection of cisplatin 8 and 20 mg/kg, respectively. We showed that cisplatin treatment significantly inhibited the expressions of OAT3, synaptophysin and microtubule-associated protein 2 (MAP2), impaired locomotor and exploration activities, and increased accumulation of uremic toxins in the brain of AKI rats and mice. In vitro studies showed that uremic toxins neither alter OAT3 expression in human cerebral microvascular endothelial cells, nor synaptophysin and MAP2 expressions in human neuroblastoma (SH-SY5Y) cells. In contrast, tumour necrosis factor alpha (TNFα) and the conditioned medium (CM) from RAW264.7 cells treated with indoxyl sulfate (IS) significantly impaired OAT3 expression. TNFα and CM from IS-treated BV-2 cells also inhibited synaptophysin and MAP2 expressions in SH-SY5Y cells. The alterations caused by TNFα and CMs in vitro, and by AKI and TNFα in vivo were abolished by infliximab, a monoclonal antibody designed to intercept and neutralize TNFα, suggesting that AKI impaired the expressions of OAT3, synaptophysin and MAP2 in the brain via IS-induced TNFα release from macrophages or microglia (termed as IS-TNFα axis). Treatment of mice with TNFα (0.5 mg·kg-1·d-1, i.p. for 3 days) significantly increased p-p65 expression and reduced the expressions of Nrf2 and HO-1. Inhibiting NF-κB pathway, silencing p65, or activating Nrf2 and HO-1 obviously attenuated TNFα-induced downregulation of OAT3, synaptophysin and MAP2 expressions. Significantly increased p-p65 and decreased Nrf2 and HO-1 protein levels were also detected in brain of AKI mice and rats. We conclude that AKI inhibits the expressions of OAT3, synaptophysin and MAP2 due to IS-induced TNFα release from macrophages or microglia. TNFα impairs the expressions of OAT3, synaptophysin and MAP2 partly via activating NF-κB pathway and inhibiting Nrf2-HO-1 pathway.

[Spatiotemporal Evolution and Influencing Factors of Ecosystem Service Value in the Yellow River Basin].

The external spatiotemporal evolution and intrinsic impact mechanisms of ecosystem service value are of great significance for understanding regional ecosystem issues and enhancing human ecological well-being. Based on grid data, this study used the equivalent factor method and NDVI to measure the ecosystem service value of the Yellow River Basin, analyzed the spatial-temporal evolution of urban ecosystem service value along the basin, and established a GWR model to explore the spatial heterogeneity of each influencing factor on the basis of determining the main influencing factors via geographic detector. The results showed that:① The ecosystem service value of the Yellow River Basin increased first, then decreased, and finally increased from 2000 to 2020, showing a spatial distribution pattern of "the south was higher than the north;" "the lower reaches were lower, and the upper and middle reaches were higher;" and the regulation service contributed the most to the ecosystem service value of the basin. ② The results of geographical exploration showed that the degree of influence of various factors was different. Social factors played the strongest role in explaining the ecosystem service value of the Yellow River Basin, followed by economic factors, and natural factors played the weakest role. The high value areas in the upper reaches were mainly related to rivers and lakes, and the high value areas in the middle reaches were mainly related to mountains. ③ The results of the GWR model showed that population density and land reclamation rate were negatively correlated with ecosystem service value, whereas average annual precipitation was positively correlated, and the effects increased from east to west. The GDP per unit area was negatively correlated with the overall ecosystem service value but positively correlated in the upstream region.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

MRI-Based Machine Learning Radiomics for Preoperative Assessment of Human Epidermal Growth Factor Receptor 2 Status in Urothelial Bladder Carcinoma.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) has recently emerged as hotspot in targeted therapy for urothelial bladder cancer (UBC). The HER2 status is mainly identified by immunohistochemistry (IHC), preoperative and noninvasive methods for determining HER2 status in UBC remain in searching. PURPOSES: To investigate whether radiomics features extracted from MRI using machine learning algorithms can noninvasively evaluate the HER2 status in UBC. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-five patients (age: 68.7 ± 10.5 years) with 14.3% females from January 2019 to May 2023 were divided into training (N = 156) and validation (N = 39) cohorts, and 43 patients (age: 67.1 ± 13.1 years) with 13.9% females from June 2023 to January 2024 constituted the test cohort (N = 43). FIELD STRENGTH/SEQUENCE: 3 T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo). ASSESSMENT: The HER2 status were assessed by IHC. Radiomics features were extracted from MRI images. Pearson correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were applied for feature selection, and six machine learning models were established with optimal features to identify the HER2 status in UBC. STATISTICAL TESTS: Mann-Whitney U-test, chi-square test, LASSO algorithm, receiver operating characteristic analysis, and DeLong test. RESULTS: Three thousand forty-five radiomics features were extracted from each lesion, and 22 features were retained for analysis. The Support Vector Machine model demonstrated the best performance, with an AUC of 0.929 (95% CI: 0.888-0.970) and accuracy of 0.859 in the training cohort, AUC of 0.886 (95% CI: 0.780-0.993) and accuracy of 0.846 in the validation cohort, and AUC of 0.712 (95% CI: 0.535-0.889) and accuracy of 0.744 in the test cohort. DATA CONCLUSION: MRI-based radiomics features combining machine learning algorithm provide a promising approach to assess HER2 status in UBC noninvasively and preoperatively. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

A novel predict method for muscular invasion of bladder cancer based on 3D mp-MRI feature fusion.

Objective. To assist urologist and radiologist in the preoperative diagnosis of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), we proposed a combination models strategy (CMS) utilizing multiparametric magnetic resonance imaging.Approach. The CMS includes three components: image registration, image segmentation, and multisequence feature fusion. To ensure spatial structure consistency of T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCE), a registration network based on patch sampling normalized mutual information was proposed to register DWI and DCE to T2WI. Moreover, to remove redundant information around the bladder, we employed a segmentation network to obtain the bladder and tumor regions from T2WI. Using the coordinate mapping from T2WI, we extracted these regions from DWI and DCE and integrated them into a three-branch dual-channel input. Finally, to fully fuse low-level and high-level features of T2WI, DWI, and DCE, we proposed a distributed multilayer fusion model for preoperative MIBC prediction with five-fold cross-validation.Main results. The study included 436 patients, of which 404 were for the internal cohort and 32 for external cohort. The MIBC was confirmed by pathological examination. In the internal cohort, the area under the curve, accuracy, sensitivity, and specificity achieved by our method were 0.928, 0.869, 0.753, and 0.929, respectively. For the urologist and radiologist, Vesical Imaging-Reporting and Data System score >3 was employed to determine MIBC. The urologist demonstrated an accuracy, sensitivity, and specificity of 0.842, 0.737, and 0.895, respectively, while the radiologist achieved 0.871, 0.803, and 0.906, respectively. In the external cohort, the accuracy of our method was 0.831, which was higher than that of the urologist (0.781) and the radiologist (0.813).Significance. Our proposed method achieved better diagnostic performance than urologist and was comparable to senior radiologist. These results indicate that CMS can effectively assist junior urologists and radiologists in diagnosing preoperative MIBC.

Role of Additional MRI-Based Morphologic Measurements on the Performance of VI-RADS for Muscle-Invasive Bladder Cancer.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. PURPOSE: To investigate additional role of morphological (MOR) measurements to VI-RADS for the detection of muscle-invasive bladder cancer (MIBC) with mpMRI. STUDY TYPE: Retrospective. POPULATION: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted imaging with fast-spin-echo sequence, spin-echo-planar diffusion-weighted imaging and dynamic contrast-enhanced imaging with fast 3D gradient-echo sequence. ASSESSMENT: VI-RADS score and MOR measurement including tumor location, number, stalk, cauliflower-like surface, type of tumor growth, tumor-muscle contact margin (TCM), tumor-longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3-year, 8-year, and 15-year experience of bladder MRI, respectively) who were blinded to histopathology. STATISTICAL TESTS: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI-RADS. A P-value <0.05 was considered statistically significant. RESULTS: TCM (OR 9.98; 95% confidence interval [CI] 4.77-20.8), TCI (OR 5.72; 95% CI 2.37-13.8), and TLL (OR 3.35; 95% CI 1.40-8.03) were independently associated with MIBC at multivariable LR analysis. VI-RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI-RADS at DCA. Specially in VI-RADS-defined equivocal lesions, MOR-based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. DATA CONCLUSION: MOR measurements improved the performance of VI-RADS in detecting MIBC with mpMRI, especially for equivocal lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

A Nomogram of MRI Features to Assess Muscle Invasion in VI-RADS 2 Tumors With Stalk.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is widely used to assess the muscle-invasive status of bladder cancer. However, the current classification efficacy of VI-RASD 2 tumors of stalk is unsatisfactory. PURPOSE: To develop a nomogram to assess muscle-invasive bladder cancer (MIBC) in VI-RADS 2 tumors with stalk. STUDY TYPE: Retrospective. POPULATION: A total of 186 patients (age: 67.8 ± 12.7 years) with 15.1% females, divided randomly into a training cohort (N = 130) and validation cohort (N = 56). FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). ASSESSMENT: Twenty-one MRI features of tumors and stalks were developed from training cohort. The mean apparent diffusion coefficient (ADC) values of the tumor, stalk, and psoas muscles were calculated from the three circular regions of interest. The normalized T value = mean ADC tumor mean ADC muscle . The normalized ST value = mean ADC stalk mean ADC tumor . Three readers assessed the morphology of tumors and stalks. STATISTICAL TESTS: The final features of nomogram were selected by univariable logistic and the least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis. RESULTS: In VI-RADS 2 tumors with stalk, tumor size over 3 cm, increased stalk width, stalk morphology, decreased normalized T value, and increased normalized ST value were selected as the risk factors for MIBC. The AUC, accuracy, sensitivity, and specificity of the nomogram to assess MIBC were 0.969 (95% CI: 0.941-0.997), 92.3%, 94.1%, and 92.0% in training cohort and 0.940 (95% CI: 0.859-1.000), 89.3%, 75.0%, and 91.7% in validation cohort. DATA CONCLUSION: This study constructed a nomogram for preoperative assessment of MIBC and modifying the current VI-RADS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

The adsorption of 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP) by lactic acid bacteria 37X-15 and its peptidoglycan.

The heterocyclic amine 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP), commonly found in roasted meat products, is considered a potential carcinogen. This study is to explore the underlying mechanisms involved in the adsorption of PhIP by lactic acid bacteria 37X-15 and its peptidoglycan. The scanning electron microscope results suggested that the strain's adsorption on PhIP occurs on the cell wall, primarily composed of peptidoglycan. The fourier-transformed infrared spectroscopy results indicated that PhIP adsorption by both lactic acid bacteria 37X-15 and its peptidoglycan primarily involved OH and NH binding groups. Different adsorption conditions affected the adsorption rate of PhIP by peptidoglycan. The optimal values for each adsorption condition were 2 h, 37 °C, and pH 6 when the maximum adsorption rate reached. This study provides a new direction for the application of lactic acid bacteria and its peptidoglycan in food safety.

Mapping the immunological battlefield in gastric cancer: prognostic implications of an immune gene expression signature.

BACKGROUND: Gastric cancer (GC) is a heterogeneous malignancy with variable clinical outcomes. The immune system has been implicated in GC development and progression, highlighting the importance of immune-related gene expression patterns and their prognostic significance. OBJECTIVE: This study aimed to identify differentially expressed immune-related genes (DEIRGs) and establish a prognostic index for GC patients using comprehensive bioinformatic analyses. METHODS: We integrated RNA sequencing data from multiple databases and identified DEIRGs by overlapping differentially expressed genes with immune-related genes. Functional enrichment analysis was performed to uncover the biological processes and signaling pathways associated with DEIRGs. We conducted a Weighted Gene Co-expression Network Analysis (WGCNA) to identify key gene modules related to with GC. Cox regression analysis was conducted to determine independent prognostic DEIRGs for overall survival prediction. Based on these findings, we developed an immune-related gene prognostic index (IRGPI) based on these findings. The prognostic value of the IRGPI was validated using survival analysis and an independent validation cohort. Functional enrichment analysis, gene mutation analysis, and immune cell profiling were performed to gain insights into the biological functions and immune characteristics associated with the IRGPI-based subgroups. RESULTS: We identified 493 DEIRGs significantly enriched in immune-related biological processes and signaling pathways associated with GC. WGCNA analysis revealed a significant module (turquoise module) associated with GC, revealing potential therapeutic targets. Cox regression analysis identified RNASE2, CGB5, CTLA4, and DUSP1 as independent prognostic DEIRGs. The IRGPI, incorporating the expression levels of these genes, demonstrated significant prognostic value in predicting overall survival. The IRGPI-based subgroups exhibited distinct biological functions, genetic alterations, and immune cell compositions. CONCLUSION: Our study identified DEIRGs and established a prognostic index (IRGPI) for GC patients. The IRGPI exhibited promising prognostic potential and provided insights into GC tumor biology and immune characteristics. These findings have implications for guiding therapeutic strategies.

Functional polymorphisms in Benzo(a)Pyrene-induced toxicity pathways associated with the risk on laryngeal squamous cell carcinoma.

Benzo(a)Pyrene (BaP) is a well-known environmental carcinogen that poses a significant risk to human health. The pivotal genes and toxicity pathways have been identified as key events to construct the mode of action (MOA) of BaP. In this study, we focused on evaluating the association between genetic variants in BaP-disturbed toxicity pathways and the susceptibility of laryngeal squamous cell carcinoma (LSCC), based on the data of our previous genome-wide association analysis (GWAS). In addition, we investigated the biological roles of these significant polymorphisms by integrating bioinformatic annotation and experimental validation. Our findings revealed that 15 functional polymorphisms in AHR signaling, p53 signaling, NRF2 signaling, TGF-ß signaling, STAT3 signaling, and IL-8 signaling pathways were significantly associated with susceptibility to LSCC. Our study provides a novel approach for identifying novel risk genetic loci utilizing GWAS data, and suggests potential targets for early detection of LSCC in the future.

The Effect of Lactiplantibacillus plantarum x3-2b Bacterial Powder on the Physicochemical Quality and Biogenic Amines of Fermented Lamb Jerky.

In this study, a protective agent was added to prepare a high-activity Lactiplantibacillus plantarum x3-2b bacterial powder as a fermentation agent and explore its effect on the physicochemical quality, biogenic amines, and flavor of fermented lamb jerky. A composite protective agent, composed of 15% skim milk powder and 10% trehalose, was used, and bacterial mud was mixed with the protective agent at a 1:1.2 mass ratio. The resulting freeze-dried bacterial powder achieved a viable count of 5.1 lg CFU/g with a lyophilization survival rate of 87.58%. Scanning electron microscopy revealed enhanced cell coverage by the composite protective agent, maintaining the cell membrane's integrity. Inoculation with x3-2b bacterial powder increased the pH and the reduction in aw, enhanced the appearance and texture of fermented lamb jerky, increased the variety and quantity of flavor compounds, and reduced the accumulation of biogenic amines (phenethylamine, histamine, and putrescine). This research provides a theoretical basis for improving and regulating the quality of lamb jerky and establishes a foundation for the development of bacterial powder for the commercial fermentation of meat products.

Big data sentiment analysis of business environment public perception based on LTP text classification --Take Heilongjiang province as an example.

At present, the research of business environment is limited to conducting surveys on specific groups or measuring data from official databases. The assessment of the business environment largely depends on public perception. Aiming to explore the public perception of business environment, this paper organically combines the big data text mining and sentiment analysis (SA). The results show that the combination of big data text mining and SA can reflect the theme characteristics, reduce the bias of sentiment and text analysis, and clearly show the public perception of the business environment. The empirical study found that the public perception of business environment depends on not only the four dimensions of business environment, but also the influence of public opinion that cannot be ignored. The public's low recognition of the business environment in Heilongjiang Province mainly includes backward economic development, serious brain drain, low government efficiency, imperfect policies, administrative law enforcement, regional climate and urban construction. In order to solve these problems, it is necessary to improve the high-standard market system to promote economic development, enhance the efficiency of government services, improve government policies, effectively enhance law enforcement, strengthen infrastructure construction and promote cultural innovation.

Solanum nigrum Linn.: Advances in anti-cancer activity and mechanism in digestive system tumors.

Cancer has currently become a serious public health issue in many countries worldwide, and tumors of the digestive system have attracted an increasing number of researchers' due to their numerous types, high proportion and wide area of occurrence. While tumors of the digestive system suffer from high mortality rates, leading to untimely diagnosis and a poor prognosis, making it necessary to update current treatment approaches such as surgery, radiation therapy, and chemotherapy. This highlights the importance of exploring novel therapeutic ideas and targets. Traditional Chinese medicine has a long history of clinical use due to its low toxicity and multi-factor targeting of multiple pathways. As a kind of traditional Chinese herb, S. nigrum Linn. is highly regarded for its proven antitumor activity. The aim of this study was to comprehensively recapitulate and analyze the anti-cancer effects and molecular mechanisms of treatment of gastrointestinal tumors with S. nigrum Linn. extracts and related compounds, including classical signaling pathways mediated by them as well as noncoding RNA pathways associated with tumor suppression. Components that have been found to be responsible for the anti-cancer activity of S. nigrum Linn. include solanine, solasonine, solamargine, a-L-rhhamnopyranose, uttroside B, degalactotigonin, glycoprotein, and other compounds. The underlying mechanisms of anti-cancer activity reflected in this study include apoptosis, cell cycle arrest, autophagy, anti-angiogenesis, suppression of metastasis and invasion, immune escape, and increased sensitivity to radiotherapy. S. nigrum Linn. has great potential in the treatment of tumors of the digestive system, and through further clinical trials and pharmacological mechanisms it has the potential to become a uniform and standardized anti-tumor drug.

A lithium superionic conductor for millimeter-thick battery electrode.

No design rules have yet been established for producing solid electrolytes with a lithium-ion conductivity high enough to replace liquid electrolytes and expand the performance and battery configuration limits of current lithium ion batteries. Taking advantage of the properties of high-entropy materials, we have designed a highly ion-conductive solid electrolyte by increasing the compositional complexity of a known lithium superionic conductor to eliminate ion migration barriers while maintaining the structural framework for superionic conduction. The synthesized phase with a compositional complexity showed an improved ion conductivity. We showed that the highly conductive solid electrolyte enables charge and discharge of a thick lithium-ion battery cathode at room temperature and thus has potential to change conventional battery configurations.

Diesel exhaust particles exposure induces liver dysfunction: Exploring predictive potential of human circulating microRNAs signature relevant to liver injury risk.

Diesel exhaust particles (DEP) pollution should be taken seriously because it is an extensive environmental and occupational health concern. Exploring early effect biomarkers is crucial for monitoring and managing DEP-associated health risk assessment. Here, we found that serum levels of 67 miRNAs were dysregulated in DEP exposure group. Notably, 20 miRNAs were identified as each having a significant dose-response relationship with the internal exposure level of DEP. Further, we revealed that the DEP exposure could affect the liver function of subjects and that 7 miRNAs (including the well-known liver injury indicator, miR-122-5p) could serve as the novel epigenetic-biomarkers (epi-biomarkers) to reflect the liver-specific response to the DEP exposure. Importantly, an unprecedented prediction model using these 7 miRNAs was established for the assessment of DEP-induced liver injury risk. Finally, bioinformatic analysis indicated that the unique set of miRNA panel in serum might also contribute to the molecular mechanism of DEP exposure-induced liver damage. These results broaden our understanding of the adverse health outcomes of DEP exposure. Noteworthy, we believe this study could shed light on roles and functions of epigenetic biomarkers from environmental exposure to health outcomes by revealing the full chain of exposure-miRNAs-molecular pathways-disease evidence.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

Genomic Characterization Revealed PM2.5-Associated Mutational Signatures in Lung Cancer Including Activation of APOBEC3B.

Fine particulate matter (PM2.5) exposure causes DNA mutations and abnormal gene expression leading to lung cancer, but the detailed mechanisms remain unknown. Here, analysis of genomic and transcriptomic changes upon a PM2.5 exposure-induced human bronchial epithelial cell-based malignant transformed cell model in vitro showed that PM2.5 exposure led to APOBEC mutational signatures and transcriptional activation of APOBEC3B along with other potential oncogenes. Moreover, by analyzing mutational profiles of 1117 non-small cell lung cancers (NSCLCs) from patients across four different geographic regions, we observed a significantly higher prevalence of APOBEC mutational signatures in non-smoking NSCLCs than smoking in the Chinese cohorts, but this difference was not observed in TCGA or Singapore cohorts. We further validated this association by showing that the PM2.5 exposure-induced transcriptional pattern was significantly enriched in Chinese NSCLC patients compared with other geographic regions. Finally, our results showed that PM2.5 exposure activated the DNA damage repair pathway. Overall, here we report a previously uncharacterized association between PM2.5 and APOBEC activation, revealing a potential molecular mechanism of PM2.5 exposure and lung cancer.