Low-level laser selectively inhibiting colorectal cancer cell metabolic activity and inducing apoptosis for delaying the development of intestinal cancer.

Low-level laser irradiation (LLLI) is a novel approach that shows promise for the treatment of colorectal cancer (CRC). However, the molecular mechanisms underlying its biochemical effects and gene expression remain unclear. Here, LLLI (632.8 nm) was used to treat CRC RKO cells and normal small intestinal NCM460 cells. LLLI showed a significant dose- and time-dependent effect on cell viability, in which a single dose of irradiation at 15 J/cm2 selectively inhibited the growth of RKO cells but largely unaffected the activity of NCM460 cells. And then, LLLI produced an internal response, effectively reducing the level of H2O2 in tumor cells, downregulating the mitochondrial membrane potential, and improving the efficiency of apoptosis in CRC, but no internal response was observed in NCM460 cells under the same conditions. Furthermore, the expression of several important genes in the classical WNT pathway was significantly downregulated, and the pathway was inactivated after LLLI intervention, thereby inhibiting tumor cell growth. Simultaneously, TNF-α was effectively activated to stimulate the caspase family members of the death effector to initiate apoptosis led by the extrinsic pathway. LLLI successfully achieves tumor cell normalization while delivering a potent anticancer effect, expected to be a novel therapeutic modality for CRC.

Tumor-derived extracellular vesicles confer 5-fluorouracil resistance in esophageal cancer via long noncoding RNA AC116025.2 delivery.

5-Fluorouracil (5-FU) resistance is one of the main causes for treatment failure in esophageal cancer (EC). Here, we intended to elucidate the mechanism of tumor-derived extracellular vesicles (TEVs)-encapsulated long noncoding RNAs (lncRNAs) AC116025.2 in 5-FU resistance in EC. EVs were isolated from the serum samples of EC patients and HEEC, TE-1, and TE-1/5-FU cells, followed by RT-qPCR detection of AC116025.2 expression in EVs. The relationship among AC116025.2, microRNA (miR)-4496, and SEMA5A was evaluated. Next, EC cells were cocultured with EVs, followed by lentivirus transduction and plasmid transfection for studying the role of TEVs-AC116025.2 in EC cells in relation to miR-4496 and SEMA5A. Tumor formation in nude mice was applied for in vivo confirmation. Elevated AC116025.2 expression was seen in the EVs from the serum of 5-FU insensitive patients and from 5-FU-resistant EC cells. Mechanistically, AC116025.2 bound to miR-4496 that inversely targeted SEMA5A in EC cells. EVs-oe-AC116025.2 augmented EC cell viability, colony formation, and 5-FU resistance, but diminished their apoptosis through miR-4496-mediated SEMA5A. Furthermore, EVs-oe-AC116025.2 augmented tumor formation and 5-FU resistance of EC cells in vivo. Conclusively, our data offered evidence of the promoting mechanism of TEVs in the 5-FU resistance of EC by delivering AC116025.2.

Genome-wide association study of 7661 Chinese Han individuals and fine-mapping major histocompatibility complex identifies HLA-DRB1 as associated with IgA vasculitis.

BACKGROUND: Immunoglobulin-A vasculitis (IgAV) is an immune-related systemic vasculitis with an unclear etiology. Genetic predisposition is now considered to be closely associated with the development of the disease, and it is essential to reveal the relationship between them. To explore the role of heredity in the disease, we performed a genome-wide association study (GWAS) of 496 IgAV cases and 7165 controls using an Illumina Infinium Global Screening Array chip. METHODS: In the first stage of analysis, a significant correlation between the major histocompatibility complex (MHC) and IgAV was observed. Subsequently, human leukocyte antigen (HLA) analysis was conducted using a new large-scale Han-MHC reference panel. Fine mapping of IgAV risk in the MHC region indicated that two amino acid positions, 120 and 11, of HLA-DRB1 and three potential HLA alleles (HLA-DRB1∗04, HLA-DRB1∗16, and HLA-DRB1∗16:02) were significantly associated. RESULTS: Further stepwise conditional analysis demonstrated that 3 amino acid positions (120, 26, 96) of HLA-DRB1 and 6 HLA-DRB1 alleles (HLA-DRB1*04, HLA-DRB1*16, HLA-DRB1*01, HLA-DRB1*12:02, HLA-DRB1*10, and HLA-DRB1*15:02) were independent signals. Among them, the most significant signal was HLA-DRB1 amino acid Ser120 (OR = 1.59, p = 3.19 × 10-8 ); no independent signal in the MHC region except for HLA-DRB1 was found. CONCLUSIONS: Our study confirms that the pathogenesis of IgAV has a genetic component and that HLA-DRB1 is strongly associated with susceptibility to IgAV.

miR-502-5p affects gastric cancer progression by targeting PD-L1.

BACKGROUND: Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer. METHODS: Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot. RESULTS: The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels. CONCLUSIONS: These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.

Suppression of SHROOM1 Improves In Vitro and In Vivo Gene Integration by Promoting Homology-Directed Repair.

Homologous recombination (HR) is often used to achieve targeted gene integration because of its higher precision and operability compared with microhomology-mediated end-joining (MMEJ) or non-homologous end-joining (NHEJ). It appears to be inefficient for gene integration in animal cells and embryos due to occurring only during cell division. Here we developed genome-wide high-throughput screening and a subsequently paired crRNA library screening to search for genes suppressing homology-directed repair (HDR). We found that, in the reporter system, HDR cells with knockdown of SHROOM1 were enriched as much as 4.7-fold than those with control. Down regulating SHROOM1 significantly promoted gene integration in human and mouse cells after cleavage by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9), regardless of the donor types. The knock-in efficiency of mouse embryos could also be doubled by the application of SHROOM1 siRNA during micro-injection. The increased HDR efficiency of SHROOM1 deletion in HEK293T cells could be counteracted by YU238259, an HDR inhibitor, but not by an NHEJ inhibitor. These results indicated that SHROOM1 was an HDR-suppressed gene and that the SHROOM1 knockdown strategy may be useful for a variety of applications, including gene editing to generate cell lines and animal models for studying gene function and human diseases.

Somatic mutations in renal cell carcinomas from Chinese patients revealed by whole exome sequencing.

BACKGROUND: While the somatic mutation profiles of renal cell carcinoma (RCC) have been revealed by several studies worldwide, the overwhelming majority of those were not derived from Chinese patients. The landscape of somatic alterations in RCC from Chinese patients still needs to be elucidated to determine whether discrepancies exist between Chinese patients and sufferers from other countries and regions. METHODS: We collected specimens from 26 Chinese patients with primary RCC, including 15 clear cell renal cell carcinoma (ccRCC) samples, 5 papillary renal cell carcinoma (PRCC) samples and 6 chromophobe renal cell carcinoma (ChRCC) samples. Genomic DNAs were isolated from paired tumor-normal tissues and subjected to whole exome sequencing (WES). Immunohistochemistry analysis was performed to detect the programmed death ligand 1 (PD-L1) expression in tumor tissues. RESULTS: A total of 1920 nonsynonymous somatic variants in exons and 86 mutations at splice junctions were revealed. The tumor mutation burden of ccRCC was significantly higher than that of ChRCC (P < 0.05). For both ccRCC and PRCC, the most frequent substitution in somatic missense mutations was T:A > A:T, which was different from that recorded in the COSMIC database. Among eight significantly mutated genes in ccRCC in the TCGA database, six genes were verified in our study including VHL (67%), BAP1 (13%), SETD2 (13%), PBRM1 (7%), PTEN (7%) and MTOR (7%). All the mutations detected in those genes had not been reported in ccRCC before, except for alterations in VHL and PBRM1. Regarding the frequently mutated genes in PRCC in our study, DEPDC4 (p.E293A, p.T279A), PNLIP (p.N401Y, p.F342L) and SARDH (p.H554Q, p.M1T) were newly detected gene mutations predicted to be deleterious. As the most recurrently mutated gene in ChRCC in the TCGA dataset, TP53 (p.R81Q) was somatically altered only in one ChRCC case in this study. The HIF-1 signaling pathway was the most affected pathway in ccRCC, while the PI3K-Akt signaling pathway was altered in all of the three RCC types. Membranous PD-L1 expression was positive in tumor cells from 6/26 (23%) RCC specimens. The PD-L1-positive rate was higher in RCC samples with the somatically mutated genes CSPG4, DNAH11, INADL and TMPRSS13 than in specimens without those (P < 0.05). CONCLUSIONS: Using WES, we identified somatic mutations in 26 Chinese patients with RCC, which enriched the racial diversity of the somatic mutation profiles of RCC subjects, and revealed a few discrepancies in molecular characterizations between our study and published datasets. We also identified numerous newly detected somatic mutations, which further supplements the somatic mutation landscape of RCC. Moreover, 4 somatically mutated genes, including CSPG4, DNAH11, INADL and TMPRSS13, might be promising predictive factors of PD-L1-positive expression in RCC tumor cells.

High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction.

Myocardial infarction (MI) is the most common cause of heart failure. Excessive production of ROS plays a key role in the pathogenesis of cardiac remodeling after MI. NADPH with NADPH oxidase (Nox)2 as the catalytic subunit is a major source of superoxide production, and expression is significantly increased in the infarcted myocardium, especially by infiltrating macrophages. While microRNAs (miRNAs) are potent regulators of gene expression and play an important role in heart disease, there still lacks efficient ways to identify miRNAs that target important pathological genes for treating MI. Thus, the overall objective was to establish a miRNA screening and delivery system for improving heart function after MI using Nox2 as a critical target. With the use of the miRNA-target screening system composed of a self-assembled cell microarray (SAMcell), three miRNAs, miR-106b, miR-148b, and miR-204, were identified that could regulate Nox2 expression and its downstream products in both human and mouse macrophages. Each of these miRNAs were encapsulated into polyketal (PK3) nanoparticles that could effectively deliver miRNAs into macrophages. Both in vitro and in vivo studies in mice confirmed that PK3-miRNAs particles could inhibit Nox2 expression and activity and significantly improve infarct size and acute cardiac function after MI. In conclusion, our results show that miR-106b, miR-148b, and miR-204 were able to improve heart function after myocardial infarction in mice by targeting Nox2 and possibly altering inflammatory cytokine production. This screening system and delivery method could have broader implications for miRNA-mediated therapeutics for cardiovascular and other diseases.NEW & NOTEWORTHY NADPH oxidase (Nox)2 is a promising target for treating cardiovascular disease, but there are no specific inhibitors. Finding endogenous signals that can target Nox2 and other inflammatory molecules is of great interest. In this study, we used high-throughput screening to identify microRNAs that target Nox2 and improve cardiac function after infarction.

RNAe: an effective method for targeted protein translation enhancement by artificial non-coding RNA with SINEB2 repeat.

In this study, a universal protein expression enhancement RNA tool, termed RNAe, was developed by modifying a recently discovered natural long non-coding RNA. At the moment, RNAe is the only technology for gene expression enhancement, as opposed to silencing, at the post-transcriptional level. With this technology, an expression enhancement of 50-1000% is achievable, with more than 200% enhancement achieved in most cases. This work identified the sufficient and necessary element for RNAe function, which was found to be merely 300 nucleotides long and was named minRNAe. It contains a 72-nt 5' pairing sequence which determines the specificity, a 167-nt short non-pairing interspersed nuclear element (SINE) B2 sequence which enhances ribosome recruitment to the target mRNA, and a poly(A) tail, provided together on a plasmid bearing the appropriate sequences. Cellular delivery of RNAe was achieved using routine transfection. The RNAe platform was validated in several widely-used mammalian cell lines. It was proven to be efficient and flexible in specifically enhancing the expression of various endogenous and exogenous proteins of diverse functions in a dose-dependent manner. Compared to the expression-inhibitory tool RNAi, the RNAe tool has a comparable effect size, with an enhancing as opposed to inhibitory effect. One may predict that this brand new technology for enhancing the production of proteins will find wide applications in both research and biopharmaceutical production.

RNAe in a transgenic growth hormone mouse model shows potential for use in gene therapy.

OBJECTIVE: RNAe is a new method that enhances protein expression at the post-transcriptional level. RNAe utility was further explored to improve endogenous protein expression. RESULTS: Transgenic mice were created by targeting RNAe to growth hormone gene into the C57/BL mouse genome by transposon mediated integration; the mice showed a heavier body weight and longer body length compared with normal mice. RNAe can also be used for gene therapy through the delivery of in vitro transcribed RNA. CONCLUSION: This study takes a further step towards applying RNAe in pharmaceutical approaches by transposon-based transgenic mice model construction and the use of in vitro transcribed RNA transfection assay.

The synergistic regulation of VEGF-mediated angiogenesis through miR-190 and target genes.

VEGF is a major contributor to angiogenesis, a vital process in normal growth and development and tumor transition. However, the current clinical efficacy of VEGF inhibitors is limited, and the molecular mechanism underlying VEGF regulation remains to be elucidated. Here we show that miR-190 directly targets a group of angiogenic effectors besides VEGF per se. Noted, these effectors can transcriptionally regulate VEGF expression in an intracellular or intercellular manner, thus demonstrating that miR-190 modulates the VEGF-mediated tumor angiogenesis at three levels. The synergistic effect of miR-190 and its target genes demonstrates a complex but apparently more stable system, allowing for the tight control of the level of VEGF. Finally, we showed that miR-190 significantly suppresses tumor metastasis, especially angiogenesis. Together, these results indicate that miR-190 is a promising antitumor target in clinical applications.

miR-19b promotes tumor growth and metastasis via targeting TP53.

Tumor suppressor TP53 (or p53) is one of the most important regulators in numerous physiological and pathological processes. Recently, the miRNA-mediated post-transcription regulation of p53 has been studied. However, systematic studies of miRNA targeting sites within the p53 gene are still a challenging task. Here, we developed a dual-color assay capable of identifying miRNA targeting sites in a certain gene, specifically p53, in a simple, direct, and robust manner. Results showed that p53 was a direct and critical target of miR-19b, but not miR-19a, regardless of sequence similarity. Overexpression of miR-19b observed in human cancer cells can diminish p53 protein levels and, subsequently, downstream components such as Bax and p21. This miR-19b-mediated p53 reduction was shown to promote cell cycle, cell migration or invasion, and repress senescence and apoptosis in vitro. Further investigation revealed that miR-19b controls tumor growth and metastasis in vivo. Therefore, it is possible that miR-19b antagomirs or sponges could be developed as therapeutic agents against tumor development.

Engineered TAL Effector modulators for the large-scale gain-of-function screening.

Recent effective use of TAL Effectors (TALEs) has provided an important approach to the design and synthesis of sequence-specific DNA-binding proteins. However, it is still a challenging task to design and manufacture effective TALE modulators because of the limited knowledge of TALE-DNA interactions. Here we synthesized more than 200 TALE modulators and identified two determining factors of transcription activity in vivo: chromatin accessibility and the distance from the transcription start site. The implementation of these modulators in a gain-of-function screen was successfully demonstrated for four cell lines in migration/invasion assays and thus has broad relevance in this field. Furthermore, a novel TALE-TALE modulator was developed to transcriptionally inhibit target genes. Together, these findings underscore the huge potential of these TALE modulators in the study of gene function, reprogramming of cellular behaviors, and even clinical investigation.

Full endoscopic laminotomy decompression versus anterior cervical discectomy and fusion for the treatment of single-segment cervical spinal stenosis: a retrospective, propensity score-matched study.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the standard procedure for the treatment of cervical spinal stenosis (CSS), but complications such as adjacent segment degeneration can seriously affect the long-term efficacy. Currently, posterior endoscopic surgery has been increasingly used in the clinical treatment of CSS. The aim of this study was to compare the clinical outcomes of single-segment CSS patients who underwent full endoscopic laminotomy decompression or ACDF. METHODS: 138 CSS patients who met the inclusion criteria from June 2018 to August 2020 were retrospectively analyzed and divided into endoscopic and ACDF groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the groups. Then, perioperative data were recorded and clinical outcomes were compared, including functional scores and imaging data. Functional scores included Visual Analog Scale of Arms (A-VAS) and Neck pain (N-VAS), Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), and imaging data included Disc Height Index (DHI), Cervical range of motion (ROM), and Ratio of grey scale (RVG). RESULTS: After PSM, 84 patients were included in the study and followed for 24-30 months. The endoscopic group was significantly superior to the ACDF group in terms of operative time, intraoperative blood loss, incision length, and hospital stay (P < 0.001). Postoperative N-VAS, A-VAS, JOA, and NDI were significantly improved in both groups compared with the preoperative period (P < 0.001), and the endoscopic group showed better improvement at 7 days postoperatively (P < 0.05). The ROM changes of adjacent segments were significantly larger in the ACDF group at 12 months postoperatively and at the last follow-up (P < 0.05). The RVG of adjacent segments showed a decreasing trend, and the decrease was more marked in the ACDF group at last follow-up (P < 0.05). According to the modified MacNab criteria, the excellent and good rates in the endoscopic group and ACDF group were 90.48% and 88.10%, respectively, with no statistically significant difference (P > 0.05). CONCLUSION: Full endoscopic laminotomy decompression is demonstrated to be an efficacious alternative technique to traditional ACDF for the treatment of single-segment CSS, with the advantages of less trauma, faster recovery, and less impact on cervical spine kinematics and adjacent segmental degeneration.

Finite element analysis of endoscopic cross-overtop decompression for single-segment lumbar spinal stenosis based on real clinical cases.

Introduction: For severe degenerative lumbar spinal stenosis (DLSS), the conventional percutaneous endoscopic translaminar decompression (PEID) has some limitations. The modified PEID, Cross-Overtop decompression, ensures sufficient decompression without excessive damage to the facet joints and posterior complex integrity. Objectives: To evaluate the biomechanical properties of Cross-Overtop and provide practical case validation for final decision-making in severe DLSS treatment. Methods: A finite element (FE) model of L4-L5 (M0) was established, and the validity was verified against prior studies. Endo-ULBD (M1), Endo-LOVE (M2), and Cross-Overtop (M3) models were derived from M0 using the experimental protocol. L4-L5 segments in each model were evaluated for the range of motion (ROM) and disc Von Mises stress extremum. The real clinical Cross-Overtop model was constructed based on clinical CT images, disregarding paraspinal muscle influence. Subsequent validation using actual FE analysis results enhances the credibility of the preceding virtual FE analysis. Results: Compared with M0, ROM in surgical models were less than 10°, and the growth rate of ROM ranged from 0.10% to 11.56%, while those of disc stress ranged from 0% to 15.75%. Compared with preoperative, the growth rate of ROM and disc stress were 2.66%-11.38% and 1.38%-9.51%, respectively. The ROM values in both virtual and actual models were less than 10°, verifying the affected segment stability after Cross-Overtop decompression. Conclusion: Cross-Overtop, designed for fully expanding the central canal and contralateral recess, maximizing the integrity of the facet joints and posterior complex, does no significant effect on the affected segmental biomechanics and can be recommended as an effective endoscopic treatment for severe DLSS.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

An integrative approach for the large-scale identification of human genome kinases regulating cancer metastasis.

Kinases become one of important groups of drug targets. To identify more kinases being potential for cancer therapy, we developed an integrative approach for the large-scale screen of functional genes capable of regulating the main traits of cancer metastasis. We first employed self-assembled cell microarray to screen functional genes that regulate cancer cell migration using a human genome kinase siRNA library. We identified 81 genes capable of significantly regulating cancer cell migration. Following with invasion assays and bio-informatics analysis, we discovered that 16 genes with differentially expression in cancer samples can regulate both cell migration and invasion, among which 10 genes have been well known to play critical roles in the cancer development. The remaining 6 genes were experimentally validated to have the capacities of regulating cell proliferation, apoptosis and anoikis activities besides cell motility. Together, these findings provide a new insight into the therapeutic use of human kinases. FROM THE CLINICAL EDITOR: This team of authors have utilized a self-assembled cell microarray to screen genes that regulate cancer cell migration using a human genome siRNA library of kinases. They validated previously known genes and identified novel ones that may serve as therapeutic targets.

An integrated chip for the high-throughput synthesis of transcription activator-like effectors.

A TALE of two assays: Transcription activator-like effectors (TALEs) are programmable proteins that can specifically recognize a DNA sequence. Previous strategies for the synthesis of TALEs were complicated and time-consuming. The solid-phase synthesis strategy demonstrated here allows quick and simple purification of the ligation product.

Acupuncture-exacerbated pyoderma gangrenosum associated with IgG multiple myeloma.

INTRODUCTION: PG is an uncommon, noninfectious neutrophilic dermatosis. Very few cases of bullous PG as the first manifestation of IgG myeloma have been reported. HE4, a novel marker for human cancers, may be a promising marker of bone destruction and disease progression in patients with hematologic malignancies and PG lesions. CASE REPORT: The authors report a case of a 49-year-old female who presented with painful patches located on the lower extremities for the past 5 months, and then had lesions that rapidly progressed to necrotic ulcers after unregulated acupuncture therapy. During the treatment procedure, underlying IgG κ-type myeloma was diagnosed. After the diagnosis was confirmed, the patient underwent chemotherapy, and the lesions started to heal and gradually showed scarring. The current report also discusses the potential value of HE4 as applied to malignancies that present with PG and bone destruction. CONCLUSIONS: Once the diagnosis of the underlying systemic disease is confirmed, patients with PG should simultaneously receive aggressive treatment for the primary disease. More emphasis should be put on HE4 regarding the progression of monoclonal gammopathy-related PG with bone destruction to provide new ideas to understand the pathogenesis of this disease.

Treatment technologies for selenium contaminated water: A critical review.

Selenium is an indispensable trace element for humans and other organisms; however, excessive selenium in water can jeopardize the aquatic environment. Investigations on the biogeochemical cycle of selenium have shown that anthropogenic activities such as mining, refinery, and coal combustion mainly contribute to aquatic selenium pollution, imposing tremendous risks on ecosystems and human beings. Various technologies thus have been developed recently to treat selenium contaminated water to reduce its environmental impacts. This work provides a critical review on the applications, characteristics, and latest developments of current treatment technologies for selenium polluted water. It first outlines the present status of the characteristics, sources, and toxicity of selenium in water. Selenium treatment technologies are then classified into three categories: 1) physicochemical separation including membrane filtration, adsorption, coagulation/precipitation, 2) redox decontamination including chemical reduction and catalysis, and 3) biological transformation including microbial treatment and constructed wetland. Details of these methods including their overall efficiencies, applicability, advantages and drawbacks, and latest developments are systematically analyzed and compared. Although all these methods are promising in treating selenium in water, further studies are still needed to develop sustainable strategies based on existing and new technologies. Perspectives on future research directions are laid out at the end.

Network pharmacology-based approach to investigate the mechanisms of Zingiber officinale Roscoe in the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDDs) are chronic neurological disorders associated with cognitive or motor dysfunction. As a common spice, Zingiber officinale Roscoe has been used as a medicine to treat a variety of NDDs. However, at the molecular level, the mechanisms of Z. officinale in treating of NDDs have not been deeply investigated. In this study, network pharmacology method, molecular docking, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the mechanisms of Z. officinale in the treatment of NDDs. After a series of biological information analyses, five core targets were obtained, including heme oxygenase 1 (HMOX1), acetylcholinesterase (AChE), nitric oxide synthase (NOS), catechol-O-methyl-transferase (COMT), and metabotropic glutamate receptor 5 (mGluR5). Compounds 75, 68, 46, 67, 69, 49, 66, 50, 34, and 64 were identified as the main components of Z. officinale in the treatment of NDDs. The crucial pathways mainly include neuroactive ligand-receptor signaling pathways, cyclic adenosine monophosphate signaling pathways, dopamine synaptic signaling pathways, and so on. Besides, in vitro experiments by AChE inhibitory activities assay and neuroprotective activities against H2 O2 -induced injury in human neuroblastoma SH-SY5Y cells validated the reliability of the results of network analysis. PRACTICAL APPLICATIONS: Zingiber officinale Roscoe is widely used as a traditional spice and herbal medicine. It contains a number of active ingredients, which have shown activities on anti-neurodegenerative diseases (NDDs). In this paper, the potential mechanism of Z. officinale in the treatment of NDDs is explored through network pharmacology, and it was verified by in vitro experiments. The mechanism was not only clarified at the system level but also proved to be effective at the biological level. The results can be used as a reference for Z. officinale in the treating of NDDs.