Research on the Performance and Computational Fluid Dynamics Numerical Simulation of Plate Air Gap Membrane Distillation Module.

Membrane distillation (MD) is widely used in the field of seawater desalination. Among its various sub-categories, air gap membrane distillation (AGMD) stands out due to its high thermal efficiency and compatibility with low-grade heat sources. This study delves into the impact of varying operating conditions on AGMD performance, employing numerical simulations which are grounded in experimental validation. The objective was to enhance the performance of AGMD, mitigate polarization phenomena, and provide a reference for optimizing membrane component design. The results show that the agreements between the simulated and the experimental values were high. When increasing the feed temperature and decreasing the coolant temperature, the impact of polarization phenomena on the performance of AGMD was reduced. The mass flux, Total Permeate Concentration (TPC), and heat flux increased by 81.69%, 36.89%, and 118.01%, respectively, when the feed temperature was increased from 50 °C to 75 °C. When the coolant temperature decreased from 22 °C to 7 °C, the mass flux increased by 37.06%. The response surface analysis revealed that the feed temperature has significant influence on AGMD performance, and there is a noticeable interaction between the feed temperature and coolant temperature. These findings will play key roles in practical applications.

Linear and non-linear relationships between body fat mass distribution and bone mineral density in adults: The NHANES, 2011-2018.

OBJECTIVE: The relationship between body fat mass and bone mineral density (BMD) remains controversial. This research aimed to explore the linear or non-linear relationship between body fat mass and BMD among adults in the United States. METHODS: This cross-sectional study identified adults aged 18 years or older in the National Health and Nutrition Examination Survey from 2011 to 2018. After adjusting for covariates, linear relationships between body fat mass and BMD in different genders were tested by generalized linear models, and potential non-linear relationships were explored by generalized additive models and piecewise linear regression models. RESULTS: The research included 4691 (57.9% of the total sample) males and 3417 (42.1% the of total sample) females. In both males and females, we found a negative association between android or total body fat mass and lumbar spine BMD and a positive association between appendicular, android, gynoid, or total body fat mass and whole body BMD (all P < 0.05). The relationships between body fat mass in all regions and lumbar spine BMD were U-shaped in males and inverted U-shaped in females (all Pnon-linear < 0.05). Inverted U-shaped relationships existed between body fat mass in all regions and whole body BMD in females (all Pnon-linear < 0.05). CONCLUSIONS: Body fat mass was negatively and linearly associated with lumbar spine BMD, but positively associated with whole body BMD. Body fat mass had a U-shaped relationship with lumbar spine BMD in males and an inverted U-shaped association with lumbar spine and whole body BMD in females.

KLF15 transcriptionally activates LINC00689 to inhibit colorectal cancer development.

Colorectal cancer is a grievous health concern, we have proved long non-coding RNA LINC00689 is considered as a potential diagnosis biomarker for colorectal cancer, and it is necessary to further investigate its upstream and downstream mechanisms. Here, we show that KLF15, a transcription factor, exhibits the reduced expression in colorectal cancer. KLF15 suppresses the proliferative and metastatic capacities of colorectal cancer cells both in vitro and in vivo by transcriptionally activating LINC00689. Subsequently, LINC00689 recruits PTBP1 protein to enhance the stability of LATS2 mRNA in the cytoplasm. This stabilization causes the suppression of the YAP1/ß-catenin pathway and its target downstream genes. Our findings highlight a regulatory network involving KLF15, LINC00689, PTBP1, LATS2, and the YAP1/ß-catenin pathway in colorectal cancer, shedding light on potential therapeutic targets for colorectal cancer therapy.

Synthesis and biological evaluation of novel bi-gold mitocans in lung cancer cells.

Mitochondria are promising drug target for cancer treatment. We previously demonstrated that a bi-gold compound BGC2a was more potent than the mono-gold drug auranofin in suppressing cancer cells due to increased gold atom number that led to higher drug accumulation in and thereby inhibition of mitochondria. To exploit the potential of this new strategy, we further designed and synthesized a series of bi-gold mitocans, the compounds targeting mitochondria. The results showed that most of the newly synthesized mitocans exhibited obviously lower IC50 than auranofin, an old drug that is repurposed in clinical trials for cancer treatment. The best mitocan C3P4 was nearly 2-fold more potent than BGC2a in human non-small cell lung cancer A549 cells and mantle cell lymphoma Jeko-1 cells, exhibiting substantial colony formation-suppressing and tumor-suppressing effects in A549 cells xenograft model. C3P4 induced apoptosis in a dose-dependent manner and arrested cell cycle at G0/G1 phase. The mechanistic study showed that C3P4 significantly increased the global reactive oxygen species and mitochondrial superoxide level, and reduced the mitochondrial membrane potential. C3P4 preferentially accumulated in mitochondria as measured by the gold content and substantially inhibited oxygen consumption rate and ATP production. These results further validated our hypothesis that targeting mitochondria would be promising to develop more potent anticancer agents. C3P4 may be further evaluated as a drug candidate for lung cancer treatment.

LINC02454 promotes thyroid carcinoma progression via upregulating HMGA2 through CREB1.

Thyroid carcinoma (THCA) is the most common malignancy in the endocrine system. Long intergenic non-coding RNA 2454 (LINC02454) exhibits an HMGA2-like expression pattern, but their relationship and roles in THCA are largely unknown. The present purpose was to delineate the roles of LINC02454 in THCA progression and its molecular mechanisms. We collected THCA tissues from patients and monitored patient survival. THCA cell colony formation, migration, and invasion were evaluated. Metastasis was evaluated by examining EMT markers through Western blotting. Gene interaction was determined with ChIP, RIP, RNA pull-down, and luciferase activity assays. A mouse model of a subcutaneous tumor was used to determine the activity of LINC02454 knockdown in vivo. We found that LINC02454 was highly expressed in THCA, and its upregulation was associated with poor survival. The knockdown of LINC02454 repressed colony formation, migration, and invasion. Moreover, loss of LINC02454 inhibited tumor growth and metastasis in mice. HMGA2 promoted LINC02454 transcription via binding to the LINC02454 promoter, and silencing of HMGA2 suppressed malignant behaviors through downregulation of LINC02454. HMGA2 was a novel functional target of LINC02454 in THCA cells, and knockdown of LINC02454-mediated anti-tumor effects was reversed by HMGA2 overexpression. Mechanically, LINC02454 promoted CREB1 phosphorylation and nuclear translocation, and CREB1 was subsequently bound to the HMGA2 promoter to facilitate its expression. LINC02454 cis-regulates HMGA2 transcription via facilitating CREB1 phosphorylation and nuclear translocation, and, in turn, HMGA2 promotes LINC02454 expression, thus accelerating thyroid carcinoma progression. Our results support therapeutic targets of LINC02454 and HMGA2 for THCA.

Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgeries, such as hepatectomy and liver transplantation. In recent years, several non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as factors involved in the pathological progression of HIRI. In this review, we summarized the latest research on lncRNAs, miRNAs and the lncRNA-miRNA regulatory networks in HIRI. DATA SOURCES: The PubMed and Web of Science databases were searched for articles published up to December 2021 using the following keywords: "hepatic ischemia-reperfusion injury", "lncRNA", "long non-coding RNA", "miRNA" and "microRNA". The bibliography of the selected articles was manually screened to identify additional studies. RESULTS: The mechanism of HIRI is complex, and involves multiple lncRNAs and miRNAs. The roles of lncRNAs such as AK139328, CCAT1, MALAT1, TUG1 and NEAT1 have been established in HIRI. In addition, numerous miRNAs are associated with apoptosis, autophagy, oxidative stress and cellular inflammation that accompany HIRI pathogenesis. Based on the literature, we conclude that four lncRNA-miRNA regulatory networks mediate the pathological progression of HIRI. Furthermore, the expression levels of some lncRNAs and miRNAs undergo significant changes during the progression of HIRI, and thus are potential prognostic markers and therapeutic targets. CONCLUSIONS: Complex lncRNA-miRNA-mRNA networks regulate HIRI progression through mutual activation and antagonism. It is necessary to screen for more HIRI-associated lncRNAs and miRNAs in order to identify novel therapeutic targets.

Utility of Tokyo Guidelines 2018 in early laparoscopic cholecystectomy for mild and moderate acute calculus cholecystitis: A retrospective cohort study.

Background: Tokyo Guidelines 2018 (TG18) proposed laparoscopic cholecystectomy (LC) for acute calculus cholecystitis (ACC) irrespective of the duration of symptoms. This retrospective study assessed the impact of utility of TG18 in early LC for ACC. Methods: From 2018 to 2020, 66 patients with mild (grade I) and moderate (grade II) ACC who underwent early surgery were studied. Subgroup analyses were based on timing of surgery and operation time. Results: A total of 32 and 34 patients were operated within and beyond 7 days since ACC onset. More patients with grade II ACC were in the beyond 7 days group (P < 0.05). More patients with enlarged gallbladder were in the within 7 days group (P < 0.05). The duration of symptoms to admission, symptoms to LC, and operation time were longer in the beyond 7 days group (P < 0.05). There were no significant differences regarding intraoperative blood loss, conversion to bail-out procedures, complication rate, hospital stay, and cost between the two groups (P > 0.05). Longer operation time was significantly associated with duration of symptoms to admission, symptoms to LC, and conversion to laparoscopic subtotal cholecystectomy (LSC) (P < 0.05). Conclusion: In a subset of carefully selected patients, applying TG18 in early LC for mild and moderate ACC results in acceptable clinical outcomes. Standardized safe steps and conversion to LSC in difficult cases are important.

LncRNA XIST Promotes Migration and Invasion of Papillary Thyroid Cancer Cell by Modulating MiR-101-3p/CLDN1 Axis.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy in the worlds. Long non-coding RNA X-inactive specific transcript (XIST) was found to upregulate in PTC tissues and cell lines. However, the molecular mechanism underlying PTC metastasis and whether XIST plays regulatory role in PTC are still largely unknown. qRT-PCR was performed to detect the expression of lncRNA XIST and mRNAs. Western blotting was carried out to detect CLDN1, MMP2, and MMP9. Transwell assay was used to detect migration and invasion. Starbase bioinformatics prediction and luciferase assay were used to validate the relationship of miR-101-3p and XIST or CLDN1. LncRNA XIST was upregulated in PTC tissues and cells. XIST knockdown suppressed migration and invasion of PTC cells. XIST could directly bind with miR-101-3p. Overexpression of miR-101-3p suppressed migration and invasion of PTC cells. CLDN1 was the target of miR-101-3p, and overexpression of CLDN1 can reverse the inhibition of cell migration and invasion by miR-101-3p, What's more, miR-101-3p inhibition and CLDN1 overexpression can reverse the affection of sh-XIST on migration and invasion of PTC cells inhibition. XIST promotes migration and invasion of papillary thyroid cancer cell via directly regulating miR-101-3p/CLDN1 axis, which is a novel mechanistic of XIST in the regulation of PTC.

LINC00689 participates in proliferation, chemoresistance and metastasis via miR-31-5p/YAP/ß-catenin axis in colorectal cancer.

As a kind of high-incidence malignant tumors in the digestive tract, colorectal cancer (CRC) has extremely morbidity and mortality in the population. LncRNAs have been proved to regulate the proliferation, chemoresistance and metastasis of tumors including CRC. LINC00689 and miR-31-5p in CRC were found misregulated in CRC by TCGA analysis. However, the mechanism of LINC00689 and miR-31-5p in regulating CRC remains unknown. The expression levels of LINC00689, miR-31-5p and LATS2 in CRC tissues and cell lines were examined by qRT-PCR assay. Cell proliferation, metastasis (including invasion and migration) were quantified by MTT assay, colony formation and Transwell assay, respectively. Western blotting assay was then performed to verify the levels of YAP/ß-catenin and metastasis-related proteins. Dual-luciferase reporter assay and RIP assay were performed to evaluate the interaction between LINC00689 (LATS2) and miR-31-5p. Moreover, the function of LINC00689 and miR-31-5p were confirmed by CRC xenograft in nude mice. LINC00689 was decreased while miR-31-5p was increased in CRC. The overexpression of LINC00689 or the knockdown of miR-31-5p inhibited cell proliferation, chemoresistance and metastasis of CRC cells. Meanwhile, the up-regulated LATS2 suppressed the activity of YAP/ß-catenin pathway to repress CRC occurrence. Silencing LATS2 reversed the inhibition effects of overexpression of LINC00689 or knockdown of miR-31-5p on proliferation, chemoresistance and metastasis of CRC cells. LINC00689 indeed acted as a miR-31-5p sponge to inhibit CRC proliferation, chemoresistance and metastasis through up-regulating LATS2 and repressing YAP/ß-catenin signaling pathway.

miR-21 promotes growth, invasion and migration of lung cancer cells by AKT/P-AKT/cleaved-caspase 3/MMP-2/MMP-9 signaling pathway.

OBJECTIVE: This study aimed to demonstrate the effects of miR-21 on the growth, migration, and invasion of lung cancer cells A549 in vitro and the possible mechanism. METHODS: In vitro cell migration and invasion potential were determined by Transwell chamber assays. FACS was used to assess the effect of miR-21 on A549 cell cycle and apoptosis. 4-6 week-old female mice were utilized to establish a lung cancer model. The pathologic biopsy was processed by H&E staining. The expression of the proteins PTEN, RECK and Caspase 3 were detected through immunohistochemy and tumor cell apoptosis was measured by TUNEL. RESULTS: Transwell chamber assays showed that the cells going through the membrane increased significantly compared to the negative control (P<0.05). The tumor volume resulting from miR-21 mimics was significantly greater than in normal mice. Serum ELISA showed that the protein expression levels of MMP-2 and MMP-9 in miR-21 overexpression group were increased significantly. In addition, H&E staining results showed that in miR-21 overexpression tissue, invasion is more severe and immunohistochemical results proved that the miR-21 overexpression group had high expression of Caspase 3 protein but the expression of PTEN and RECK were decreased. TUNEL experiments show that increased the expression of miR-21 can inhibit the apoptosis of tumor cells. CONCLUSION: MicroRNA-21 promotes the proliferation of lung cancer cells and inhibits the apoptosis of lung cancer cells by the AKT/P-AKT/cleaved-caspase 3/MMP-2/MMP-9 signaling pathway.

New tranylcypromine derivatives containing sulfonamide motif as potent LSD1 inhibitors to target acute myeloid leukemia: Design, synthesis and biological evaluation.

Lysine-specific demethylase 1 (LSD1) is frequently elevated in acute myeloid leukemia (AML) and often leads to tumorigenesis. In recent years, numerous LSD1 inhibitors based on tranylcypromine (TCP) scaffolding have reached clinical trials. Most TCP derivatives were modified at the amino site of cyclopropane motif. Herein, we for the first time introduced a sulfonamide group in TCP benzene ring of series a compounds and performed a systematical study on structure and activity relationships by varying sulfonamide groups. The introduction of sulfonamide significantly increased the targeting capacity of TCP against LSD1. Moreover, we discovered that the Boc attached LSD1 inhibitors (labelled as series b compounds) substantially improved their anti-proliferation capacity towards AML cells. The intracellular thermal shift and LC-MS/MS results implied that Boc enhanced the drug lipophilicity and might be removed under the cancerous acidic environment to release the real pharmacophore, evidenced by the fact that a structurally similar but acidic inert pivaloyl to replace Boc dramatically dropped the cellular anti-proliferation effect. Finally, a benzyl group installed at the amino site to appropriately increase lipophilicity led to trans-4-(2-(benzylamino)-cyclopropyl)-N,N-diethylbenzenesulfonamide a10 that showed better anti-proliferation activity in AML cells and enzymatic inhibition against LSD1. Taken together, our work offers a novel TCP-based structure and provides a prodrug strategy for the discovery of potent LSD1 inhibitors by having appropriate lipophilicity.

Heterocyclic Iodoniums for the Assembly of Oxygen-Bridged Polycyclic Heteroarenes with Water as the Oxygen Source.

A diverse set of novel heterocyclic iodoniums was synthesized for the first time. The reactions of these unique iodoniums with environmentally benign water as the oxygen source provided structurally complex oxygen-incorporated heteropolycycles that are essential motifs in natural products and biologically active compounds. The transformation only required low-cost copper acetate. Further derivatization of the obtained polycycles expanded the structural diversity, which is important in the building of chemical libraries for drug discovery.

Domino Carbopalladation/C-H Activation as a Quick Access to Polycyclic Frameworks.

A new type of domino reaction for synthesis of heterocycles fusing the important bioactive cores, such as oxindole, indoline, and isoquinoline, is presented. Upon exposure to the very common palladium catalyst, the conceptually designed N-alkenyl iodobiaryls undergo a sequential carbopalladation/C-H activation to build polycyclic frameworks. These novel unique frameworks may provide structure sources in fragment-based drug discovery.

Design, synthesis and biological evaluation of N-arylsulfonyl carbazoles as novel anticancer agents.

In this work, a set of structurally diverse synthetic carbazoles was screened for their anticancer activities. According to structure-activity relationship studies, carbazoles with an N-substituted sulfonyl group exhibited better anticancer activity. Moreover, compound 8h was discovered to show the most potent anticancer effects on Capan-2 cells by inducing apoptosis and cell cycle arrest in G2/M phase. Finally, the in vivo study demonstrated that 8h prevented the tumor growth in PANC-1 and Capan-2 xenograft models without apparent toxicity.

Solvent extraction for heavy crude oil removal from contaminated soils.

A new strategy of heavy crude oil removal from contaminated soils was studied. The hexane-acetone solvent mixture was used to investigate the ability of solvent extraction technique for cleaning up soils under various extraction conditions. The mixtures of hexane and acetone (25 vol%) were demonstrated to be the most effective in removing petroleum hydrocarbons from contaminated soils and approx 90% of saturates, naphthene aromatics, polar aromatics, and 60% of nC(7)-asphaltenes were removed. Kinetic experiments demonstrated that the equilibrium was reached in 5 min and the majority of the oil pollutants were removed within 0.5 min. The effect of the ratio between solvent and soil on the extraction efficiency was also studied and results showed that the efficiency would increase following the higher solvent soil ratio. Then the multistage continuous extraction was considered to enhance the removal efficiency of oil pollutants. Three stages crosscurrent and countercurrent solvent extraction with the solvent soil ratio 6:1 removed 97% oil contaminants from soil. Clearly the results showed that the mixed-solvent of hexane and acetone (25 vol%) with character of low-toxic, acceptable cost and high efficiency was promising in solvent extraction to remove heavy oil fractions as well as petroleum hydrocarbons from contaminated soils.

Chemical composition and antimicrobial activity of the essential oils from Chloranthus japonicus Sieb. and Chloranthus multistachys Pei.

We examined the composition and antimicrobial activity of two essential oils from Chloranthus japonicus Sieb. and Chloranthus multistachys Pei. GC-FID and GC-MS analyses identified 48 and 39 compounds, which represented 95.56% and 94.58%, respectively, of all components in these oils. Of these, 28 compounds were common to both, with a relatively high amount of oxygenated monoterpenes (50.95% and 39.97%). Antimicrobial properties were evaluated in vitro via disc diffusion and microbroth dilution assays. Activities were strong against most tested microorganisms, with inhibition zones ranging from 8.1 to 22.2 mm. For both species, minimum values for inhibitory and bactericidal concentrations were 0.39 to 12.50 mg/mL and 0.78 to 50.00 mg/mL, respectively. These results suggest that these essential oils are potent natural sources of antimicrobial agents for the medicinal and pharmaceutical industries.