Cocconeiscrisscrossis sp. nov., a new monoraphid diatom (Bacillariophyta) from southern China.

A novel monoraphid diatom species, Cocconeiscrisscrossis You, Yu, Kociolek & Wang, sp. nov. is examined and described from the Qingyi River and Maolan Nature Reserve of southern China. The morphological description is based on light microscopy and scanning electron microscopy observations and the new species is compared with similar taxa in this genus. The characteristics unique to Cocconeiscrisscrossissp. nov. include its central area extending irregularly to both sides, it having closed valvocopulae with heavily silicified fimbriate margins and poles of the valvocopulae have 'sword-shaped' siliceous extensions. These features differentiate this new species from others in the genus. This new species was found in alkaline waterbodies, including streams, waterfall and ponds. It was usually found as an epiphyte on the stones; however, it was present on other substrates such as mosses.

YTHDC1-dependent m6A modification modulated FOXM1 promotes glycolysis and tumor progression through CENPA in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) exhibits heightened aggressiveness compared with other breast cancer (BC) subtypes, with earlier relapse, a higher risk of distant metastasis, and a worse prognosis. Transcription factors play a pivotal role in various cancers. Here, we found that factor forkhead box M1 (FOXM1) expression was significantly higher in TNBC than in other BC subtypes and normal tissues. Combining the findings of Gene Ontology (GO) enrichment analysis and a series of experiments, we found that knockdown of the FOXM1 gene attenuated the ability of TNBC cells to proliferate and metastasize both in vivo and in vitro. In addition, Spearman's test showed that FOXM1 significantly correlated with glycolysis-related genes, especially centromere protein A (CENPA) in datasets (GSE76250, GSE76124, GSE206912, and GSE103091). The effect of silencing FOXM1 on the inhibition of CENPA expression, TNBC proliferation, migration, and glycolysis could be recovered by overexpression of CENPA. According to MeRIP, the level of m6A modification on FOMX1 decreased in cells treated with cycloleucine (a m6A inhibitor) compared with that in the control group. The increase in FOXM1 expression caused by YTHDC1 overexpression could be reversed by the m6A inhibitor, which indicated that YTHDC1 enhanced FOXM1 expression depending on m6A modification. Therefore, we concluded that the YTHDC1-m6A modification/FOXM1/CENPA axis plays an important role in TNBC progression and glycolysis.

Hydrogen ameliorates endotoxin-induced acute lung injury through AMPK-mediated bidirectional regulation of Caspase3.

Septic lung injury is characterized by uncontrollable inflammatory infiltrations and acute onset bilateral hypoxemia. Evidence has emerged of the beneficial effect of hydrogen in acute lung injury (ALI), but the underlying mechanism is unclear. In this research, the recovery action of hydrogen on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells was investigated. The 7-day survival rate and body weight of mice were measured after intraperitoneal injection of LPS. Lung function was determined by a whole body plethysmography (WBP) system using the indicators respiratory rate and enhanced pause. Hematoxylin and eosin (HE) staining confirmed the signs of pulmonary edema and inflammatory ooze. Reverse transcription-polymerase chain reaction (RT-PCR) quantification was used to detect the expression of inflammatory factors. Western blotting analysis evaluated the expression levels of involved proteins in the AMP-activated protein kinase (AMPK) pathway. The experimental results confirmed that hydrogen provided an essential solution to the dissipative effects of LPS on survival rate, weight loss and lung function. The LPS-stimulated inflammatory factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also suppressed by hydrogen in A549 cells. Western blot analysis showed that hydrogen significantly upregulated the levels of phosphorylated AMPK (p-AMPK) and lowered the LPS-induced increased expression of dynamin-related protein 1 (Drp1) and Caspase3. These findings prove that hydrogen attenuated LPS-treated ALI by activating the AMPK pathway, supporting the feasibility of hydrogen treatment for sepsis.

Early postoperative interventions in the prevention and management of thyroidectomy scars.

Thyroidectomy scars, located on the exposed site, can cause distress in patients. Owing to the cosmetic importance of thyroidectomy scars, many studies have been conducted on its prevention and treatment. Scar formation factors mainly include inflammatory cell infiltration, angiogenesis, fibroblast proliferation, secretion of cytokines such as transforming growth factor (TGF)-ß1, and mechanical tension on the wound edges. Anti-scar methods including topical anti-scar agents, skin tension-bearing devices, and local injections of botulinum toxin, as well as lasers and phototherapies, that target these scar formation factors have been developed. However, current studies remain fragmented, and there is a lack of a comprehensive evaluation of the impacts of these anti-scar methods on treating thyroidectomy scars. Early intervention is a crucial but often neglected key to control hyperplastic thyroidectomy scars. Therefore, we review the currently adopted early postoperative strategies for thyroidectomy scar reduction, aiming to illustrate the mechanism of these anti-scar methods and provide flexible and comprehensive treatment selections for clinical physicians to deal with thyroidectomy scars.

Magnesium hydride attenuates intestinal barrier injury during hemorrhage shock by regulating neutrophil extracellular trap formation via the ROS/MAPK/PAD4 pathway.

Magnesium hydride (MgH2) is a hydrogen storage material that is known for its high capacity and safety and is capable of releasing hydrogen in a controlled manner when administered orally. This release of hydrogen has been associated with a range of biological effects, including anti-inflammatory properties, antioxidant activity, and protection of the intestinal barrier. Previous research has shown that neutrophil extracellular traps (NETs) play a role in the dysfunction of the intestinal barrier in conditions such as sepsis and critical illnesses. However, it remains unclear as to whether MgH2 can protect the intestinal barrier by inhibiting NET formation, and the underlying mechanisms have yet to be elucidated. A rat model of hemorrhagic shock was created, and pretreatment or posttreatment procedures with MgH2 were performed. After 24 h, samples from the small intestine and blood were collected for analysis. In vitro, human neutrophils were incubated with either phorbol-12-myristate-13-acetate (PMA) or MgH2. Reactive oxygen species generation and the expression of key proteins were assessed. The results demonstrated that MgH2 administration led to a decrease in inflammatory cytokines in the serum and mitigated distant organ dysfunction in rats with HS. Furthermore, MgH2 treatment reversed histopathological damage in the intestines, improved intestinal permeability, and enhanced the expression of tight junction proteins (TJPs) during HS. Additionally, MgH2 treatment was found to suppress NET formation in the intestines. In vitro pretreatment with MgH2 alleviated intestinal monolayer barrier disruption that was induced by NETs. Mechanistically, MgH2 pretreatment reduced ROS production and NET formation, inhibited the activation of ERK and p38, and suppressed the expression of the PAD4 protein. These findings indicated that MgH2 may inhibit NET formation in a ROS/MAPK/PAD4-dependent manner, which reduces NET-related intestinal barrier damage, thus offering a novel protective role in preventing intestinal barrier dysfunction during HS.

Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery / 中国药理学通报

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Sequence-Guided Localization of DNA Hybridization Enables Highly Selective and Robust Genotyping.

Genetic variations are always related to human diseases or susceptibility to therapies. Nucleic acid probes that precisely distinguish closely related sequences become an indispensable requisite both in research and clinical applications. Here, a Sequence-guided DNA LOCalization for leaKless DNA detection (SeqLOCK) is introduced as a technique for DNA hybridization, where the intended targets carrying distinct "guiding sequences" act selectively on the probes. In silicon modeling, experimental results reveal considerable agreement (R2  = 0.9228) that SeqLOCK is capable of preserving high discrimination capacity at an extraordinarily wide range of target concentrations. Furthermore, SeqLOCK reveals high robustness to various solution conditions and can be directly adapted to nucleic acid amplification techniques (e.g., polymerase chain reaction) without the need for laborious pre-treatments. Benefiting from the low hybridization leakage of SeqLOCK, three distinct variations with a clinically relevant mutation frequency under the background of genomic DNA can be discriminated simultaneously. This work establishes a reliable nucleic acid hybridization strategy that offers great potential for constructing robust and programmable systems for molecular sensing and computing.

Polyphyllin VII induces CTC anoikis to inhibit lung cancer metastasis through EGFR pathway regulation.

Circulating tumor cells (CTCs) are cells that detach from the primary tumor and enter the bloodstream, playing a crucial role in the metastasis of lung cancer. Unfortunately, there is currently a lack of drugs specifically designed to target CTCs and prevent tumor metastasis. In this study, we present evidence that polyphyllin VII, a potent anticancer compound, effectively inhibits the metastasis of lung cancer by inducing a process called anoikis in CTCs. We observed that polyphyllin VII had significant cytotoxicity and inhibited colony formation, migration, and invasion in both our newly established cell line CTC-TJH-01 and a commercial lung cancer cell line H1975. Furthermore, we found that polyphyllin VII induced anoikis and downregulated the TrkB and EGFR-MEK/ERK signaling pathways. Moreover, activation of TrkB protein did not reverse the inhibitory effect of polyphyllin VII on CTCs, while upregulation of EGFR protein effectively reversed it. Furthermore, our immunodeficient mouse models recapitulated that polyphyllin VII inhibited lung metastasis, which was associated with downregulation of the EGFR protein, and reduced the number of CTCs disseminated into the lungs by inducing anoikis. Together, these results suggest that polyphyllin VII may be a promising compound for the treatment of lung cancer metastasis by targeting CTCs.

Comparative secretomic and proteomic analysis reveal multiple defensive strategies developed by Vibrio cholerae against the heavy metal (Cd2+, Ni2+, Pb2+, and Zn2+) stresses.

Vibrio cholerae is a common waterborne pathogen that can cause pandemic cholera in humans. The bacterium with heavy metal-tolerant phenotypes is frequently isolated from aquatic products, however, its tolerance mechanisms remain unclear. In this study, we investigated for the first time the response of such V. cholerae isolates (n = 3) toward the heavy metal (Cd2+, Ni2+, Pb2+, and Zn2+) stresses by comparative secretomic and proteomic analyses. The results showed that sublethal concentrations of the Pb2+ (200 µg/mL), Cd2+ (12.5 µg/mL), and Zn2+ (50 µg/mL) stresses for 2 h significantly decreased the bacterial cell membrane fluidity, but increased cell surface hydrophobicity and inner membrane permeability, whereas the Ni2+ (50 µg/mL) stress increased cell membrane fluidity (p < 0.05). The comparative secretomic and proteomic analysis revealed differentially expressed extracellular and intracellular proteins involved in common metabolic pathways in the V. cholerae isolates to reduce cytotoxicity of the heavy metal stresses, such as biosorption, transportation and effluxing, extracellular sequestration, and intracellular antioxidative defense. Meanwhile, different defensive strategies were also found in the V. cholerae isolates to cope with different heavy metal damage. Remarkably, a number of putative virulence and resistance-associated proteins were produced and/or secreted by the V. cholerae isolates under the heavy metal stresses, suggesting an increased health risk in the aquatic products.

Discovery of Novel Mono-Carbonyl Curcumin Derivatives as Potential Anti-Hepatoma Agents.

Curcumin possesses a wide spectrum of liver cancer inhibition effects, yet it has chemical instability and poor metabolic properties as a drug candidate. To alleviate these problems, a series of new mono-carbonyl curcumin derivatives G1-G7 were designed, synthesized, and evaluated by in vitro and in vivo studies. Compound G2 was found to be the most potent derivative (IC50 = 15.39 µM) compared to curcumin (IC50 = 40.56 µM) by anti-proliferation assay. Subsequently, molecular docking, wound healing, transwell, JC-1 staining, and Western blotting experiments were performed, and it was found that compound G2 could suppress cell migration and induce cell apoptosis by inhibiting the phosphorylation of AKT and affecting the expression of apoptosis-related proteins. Moreover, the HepG2 cell xenograft model and H&E staining results confirmed that compound G2 was more effective than curcumin in inhibiting tumor growth. Hence, G2 is a promising leading compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.

How to better select SARS-CoV-2 preservation solution of virus nucleic acid testing.

BACKGROUND: Sampling and testing for SARS-CoV-2 is a widely recognized method for identifying patients with COVID-19. However, there is limited research available on the stability of nucleic acids in viral storage solutions. METHODS: This paper investigates the components that provide better protection for virus and nucleic acid detection. The study utilized real-time quantitative fluorescent PCR to detect SARS-CoV-2 and evaluate the preservation effect and stability of SARS-CoV-2 viral storage solution under various conditions, including different guanidinium salts, brands, and storage conditions. RESULTS: All brands of inactivated virus preservation solutions demonstrated effective preservation and stability. However, 0.5 mol/L guanidine hydrochloride and guanidine isothiocyanate solutions exhibited poor antiseptic effects. Additionally, refrigerated storage showed better preservation compared to room temperature storage. CONCLUSIONS: We recommend using inactivated virus collection solution to preserve and transport samples and testing preferably within 6 hours to reduce false negatives of NAT results.

Probing the processing of facial expressions in monkeys via time perception and eye tracking.

Accurately recognizing facial expressions is essential for effective social interactions. Non-human primates (NHPs) are widely used in the study of the neural mechanisms underpinning facial expression processing, yet it remains unclear how well monkeys can recognize the facial expressions of other species such as humans. In this study, we systematically investigated how monkeys process the facial expressions of conspecifics and humans using eye-tracking technology and sophisticated behavioral tasks, namely the temporal discrimination task (TDT) and face scan task (FST). We found that monkeys showed prolonged subjective time perception in response to Negative facial expressions in monkeys while showing longer reaction time to Negative facial expressions in humans. Monkey faces also reliably induced divergent pupil contraction in response to different expressions, while human faces and scrambled monkey faces did not. Furthermore, viewing patterns in the FST indicated that monkeys only showed bias toward emotional expressions upon observing monkey faces. Finally, masking the eye region marginally decreased the viewing duration for monkey faces but not for human faces. By probing facial expression processing in monkeys, our study demonstrates that monkeys are more sensitive to the facial expressions of conspecifics than those of humans, thus shedding new light on inter-species communication through facial expressions between NHPs and humans.

The rs9402373 polymorphism of CTGF gene may not be related to inflammatory bowel disease susceptibility in Chinese population based on ARMS-PCR genotyping.

Background: It has been confirmed that the connective tissue growth factor (CTGF) gene rs9402373 polymorphism is associated with fibrotic and inflammatory diseases. However, studies on the relationship between polymorphisms in CTGF rs9402373 and inflammatory bowel disease (IBD) remain rare. Therefore, the aim of this study was to assess the association between the CTGF rs9402373 polymorphism and IBD susceptibility in a Chinese population. Materials and methods: To establish an amplification refractory mutation system (ARMS) PCR technology for genotyping CTGF gene rs9402373 polymorphism, we designed two specific forward primers for the wild and mutant types by placing the allele-specific nucleotide at the penultimate position of the '3' end of the primer. Then, 10 samples were randomly selected and rechecked by DNA sequencing to verify the accuracy of this method. We further used the established method to detect specimens collected from 191 patients with inflammatory bowel disease, including 120 Crohn's disease (CD) and 71 ulcerative colitis (UC), and 110 healthy Han Chinese individuals. Results: We successfully established the ARMS-PCR method for genotyping, and the results of 10 randomly selected samples were completely consistent with DNA sequencing. The rs9402373 G allele frequencies in UC and CD cases were 38.03% and 43.75%, respectively, and in controls, they were 41.82%. No significant difference was found in minor allele frequencies between the UC or CD and control groups (P = 0.473, P = 0.676). Genotype analysis demonstrated that there was no relationship between CTGF rs9402373 polymorphism and the risk of IBD regardless of the inheritance mode (P > 0.05). Conclusions: In this preliminary study, we successfully developed a simple, efficient and cost-effective method for genotyping CTGF rs9402373 polymorphism. The polymorphism may not be related to IBD susceptibility in the Chinese Han population.

Dynamics simulation and in vitro studies of betulinic acid derivative with liver X receptor.

Molecular dynamics simulation of the dominant conformational conjugate was performed for 40 ns and 100 ns via Amber software based on molecular docking by Sybyl software. Because the RMSD and RMSF of 100 ns MD simulation were higher than that of 40 ns MD simulation, the 40 ns was reasonable and credible for MD simulation. The binding free energy and decomposition free energy of the two systems of betulinic acid, com3 with liver X receptor was calculated by the MM_GBSA and MM_PBSA methods, respectively. The results showed that the two systems reached equilibrium and convergence at 20 ns, both stable at about 2 Å, and exhibited low volatility in the range of amino acid 270 to 370 (RMSF <1 Å). The binding energy of com3 (ΔGbind = -68.02 kcal/mol by the MM_GBSA method or -55.50 kcal/mol by the MM_PBSA method) with the liver X receptor was lower than that of betulinic acid (ΔGbind = -55.70 kcal/mol or -42.73 kcal/mol) respectively, and van der Waals force was the most important main driving force, which was consistent with molecular docking and previous experiments. Hydrophobic groups and aromatic rings can be introduced appropriately in structure optimization to increase the van der Waals force and π-π accumulation effect of betulinic acid and liver X receptor, which is conducive to binding and thereby increasing antitumor activity. The clone formation assay and results of western blotting indicated that BA derivative com3 exposure inhibited cell proliferation may relate to the regulation of the AKT/mTOR pathway in 7721 cells. This study clarifies the dynamic interaction mode and potential mechanism of betulinic acid and its derivatives with the liver X receptor, which provides a new idea for the rapid screening of liver X receptor agonists from traditional Chinese medicines.Communicated by Ramaswamy H. Sarma.

Qualitative and quantitative analysis of the chemical components in Yuquan capsules by using ultra-performance liquid chromatography-mass spectrometry.

The Yuquan capsules is a commonly used traditional Chinese Patent Medicine used for the treatment of diabetes mellitus. In this study, a high-throughput analytical method for identifying the chemical composition of Yuquan capsules was established for the first time by using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry. The data obtained were subjected to fragment analysis and this was combined with UNIFI processing of natural products. One-hundred sixteen compounds were characterized from Yuquan capsules. Twelve of the bioactive compounds were quantitatively analyzed by ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry. This study was undertaken to obtain a comprehensive chemical profile analysis as well as to evaluate the overall quality of Yuquan capsules. The results will provide a reference for the quality evaluation of different Yuquan preparations. In addition, the data will enable basic pharmacodynamic research into these extensively used capsules.

Effect and mechanism of hydrogen-rich bath on mice with imiquimod-induced psoriasis.

The purpose of this study was to investigate whether hydrogen-rich bath has therapeutic effect on psoriasis and its molecular mechanism. Mice with imiquimod-induced psoriasis were established and divided into groups. The mice were respectively treated with hydrogen-rich water bath and distilled water bath. The changes of skin lesions and PSI scores of mice were compared after their treatments. HE staining was used to observe the pathological feature. The changes of inflammatory indexes and immune factors were analysed by ELISA and immunohistochemical staining. Malondialdehyde (MDA) content was measured by the thiobarbituric assay (TBA) method. By naked eye, the severity of skin lesions in hydrogen-rich water bath group was lower than that in distilled water bath group, and the psoriasis severity index (PSI) was lower (p < 0.01). The results of HE staining showed that the mice with distilled water bath had more abnormal keratosis, thickening of the spinous layer and prolongation of the dermal process, and more Munro abscess than the mice with hydrogen-rich water bath. During the course of disease, the overall levels and peaks of IL-17, IL-23, TNF-α, CD3+ and MDA in mice with hydrogen-rich bath were lower than those in mice with distilled water bath (p < 0.05). In the skin, the mice treated with the hydrogen-rich water bath also had lower peak of proliferating cell nuclear antigen (PCNA) levels. It is concluded that hydrogen-rich water bath can inhibit psoriasis inflammation and oxidative stress, relieve psoriasis skin lesions and accelerate the end of abnormal skin proliferation state, which shows a therapeutic and improving effect on psoriasis.

Transcriptome analysis reveals tumor antigen and immune subtypes of melanoma.

Purpose: To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes. Methods: Transcriptional data (HTSEQ-FPKM) and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma (SKCM) were downloaded from the UCSC XENA website (http://xena.ucsc.edu/). Subsequently, transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus (GEO), a large global public database. All the transcriptome expression data matrices were log2 transformed for subsequent analysis. GEPIA, TIMER, and IMMPORT databases are also used for analysis. Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375. Results: Our study provides potential tumor antigens for vaccine development in melanoma patients: GZMB, GBP4, CD79A, APOBEC3F, IDO1, JCHAIN, LAG3, PLA2G2D, XCL2. In addition, we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination. In view of the unclear role of IDO1 in melanoma, we selected IDO1 for cell assay validation. Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line. After IDO1 knockdown, the activity, invasion, migration and healing ability of A375 cell lines were significantly decreased. Conclusion: Our study could provide a reference for the development of vaccines for melanoma patients.

Identification of Antibacterial Components and Modes in the Methanol-Phase Extract from a Herbal Plant Potentilla kleiniana Wight et Arn.

The increase in bacterial resistance and the decline in the effectiveness of antimicrobial agents are challenging issues for the control of infectious diseases. Traditional Chinese herbal plants are potential sources of new or alternative medicine. Here, we identified antimicrobial components and action modes of the methanol-phase extract from an edible herb Potentilla kleiniana Wight et Arn, which had a 68.18% inhibition rate against 22 species of common pathogenic bacteria. The extract was purified using preparative high-performance liquid chromatography (Prep-HPLC), and three separated fragments (Fragments 1-3) were obtained. Fragment 1 significantly elevated cell surface hydrophobicity and membrane permeability but reduced membrane fluidity, disrupting the cell integrity of the Gram-negative and Gram-positive pathogens tested (p < 0.05). Sixty-six compounds in Fragment 1 were identified using Ultra-HPLC and mass spectrometry (UHPLC-MS). The identified oxymorphone (6.29%) and rutin (6.29%) were predominant in Fragment 1. Multiple cellular metabolic pathways were altered by Fragment 1, such as the repressed ABC transporters, protein translation, and energy supply in two representative Gram-negative and Gram-positive strains (p < 0.05). Overall, this study demonstrates that Fragment 1 from P. kleiniana Wight et Arn is a promising candidate for antibacterial medicine and food preservatives.