Design of Anti-Hund Organic Emitters Based on Heptazine.

Hund's rule, which is powerful in governing the first excited states of closed-shell organic materials, can hardly be violated to get inverted singlet-triplet gap (INVEST) molecules with negative singlet-triplet energy gaps (ΔEST), although INVEST materials have shown extraordinary photophysical properties and promising device performance especially in light-emitting diodes. Here, we propose a facile strategy to construct emissive INVEST molecules by introducing different types of substituents to heptazine in various modes, which can effectively tune the ΔEST to be negative with the enlarged oscillator strength (f) for the high fluorescence rate of the heptazine derivatives. Systematic computational studies show that the double substitution of electron-donating units with another nonconjugated substituent in hybrid substitution mode is the most favorable way in achieving slightly negative ΔEST and large f values; the conjugated substituent will compete with heptazine to make the molecule deviate from the INVEST feature. Especially, a series of high-performance heptazine-based INVEST emitters were constructed, exhibiting ΔEST low to -0.362 eV, f up to 0.0436, as well as a wide range emission color from 339 to 716 nm. Also, the designed molecules were predicted to have fluorescence radiative rates up to 106 s-1, along with efficient reverse intersystem crossing rates reaching 108 s-1. Importantly, the figure of merit (FM) was first proposed as a parameter to wholly evaluate the performance of INVEST emitters, and the highest FM of 0.198 was found in the triazine and double nonconjugated amine-substituted heptazine. These results highlight the great potential of the heptazine chromophore in constructing INVEST emitters, revealing fundamental structure-property understandings for the material design of efficient anti-Hund organic molecules with improved emission properties.

miR-605-3p may affect caerulein-induced ductal cell injury and pyroptosis in acute pancreatitis by targeting the DUOX2/NLRP3/NF-κB pathway.

Acute pancreatitis (AP) is a sudden-onset disease of the digestive system caused by abnormal activation of pancreatic enzymes. Dual oxidase 2 (DUOX2) has been found to be elevated in the progression of a variety of inflammatory diseases. Therefore, we analyzed the specific roles of DUOX2 in AP development. Blood samples were collected from of AP patients and healthy people, and the caerulein- stimulated human pancreatic duct cells (H6C7) were utilized to establish an AP cell model. Cell growth and apoptosis were measured using an MTT assay and TUNEL staining. Additionally, RT-qPCR and western blot assays were conducted to assess the RNA and protein expressions of the cells. ELISA kits were used to determine TNF-α, IL-6, IL-8, and IL-1ß levels. The interaction between DUOX2 and miR-605-3p was predicted using the Targetscan database and confirmed by dual-luciferase report assay. We found that DUOX2 increased while miR-605-3p decreased in the blood of AP patients and caerulein-stimulated H6C7 cells. DUOX2 was targeted by miR-605-3p. Furthermore, DUOX2 knockdown or miR-605-3p overexpression promoted cell viability, decreased the TNF-α, IL-6, IL-8, and IL-1ß levels, and inhibited apoptosis rate in caerulein-stimulated H6C7 cells. DUOX2 knockdown or miR-605-3p overexpression also increased the Bcl-2 protein levels and down-regulated Bax, cleaved-caspase-1, NLRP3 and p-p65. Interestingly, DUOX2 overexpression reversed the miR-605-3p mimic function in the caerulein-treated H6C7 cells. In conclusion, our research demonstrated that DUOX2 knockdown relieved the injury and inflammation in caerulein-stimulated H6C7 cells.

Multi-Stimuli-Responsive Carbon Dots with Intrinsic Photochromism and In Situ Radical Afterglow.

The combination of advanced photoluminescence characteristics to photochromism is highly attractive in preparing high-performance multifunctional photo-responsive materials for optoelectronic applications. However, this is rather challenging in material design owing to the limited mechanism understanding and construction principles. Here, an effective strategy to integrate photochromism and afterglow emission in carbon dots (CDs) is proposed through embedding naphthaleneimide (NI) structure in CDs followed by polyvinylpyrrolidone (PVP) encapsulation. The NI-structured CDs-PVP shows intrinsic photochromism owing to the in situ formation of NI-radical anions and controllable multi-stimuli-responsive afterglow behaviors related to the oxygen-trigged triplet exciton quenching and Förster resonance energy transfer (FRET) from the pristine CDs to the photoactivated CDs radicals. Notably, a wide range of appearance colors from colorless to brown, luminescence color transition from blue to yellow, and much elongated afterglow lifetime up to 253 ms are observed. With the extraordinary stimuli-chromic and stimuli-luminescent CDs-PVP film dynamically responsive to multiple external stimuli, reversible secure snapchat, data encryption/decryption and synaptic imaging recognition are realized. These findings demonstrate a fundamental principle to design multi-stimuli-responsive photochromic CDs with afterglow, providing important understandings on the synergic mechanism of dynamic photochromism and emission behaviors and thereby expanding their applications in advanced information anti-counterfeiting and artificial intelligence.

Tidal control on aerobic methane oxidation and mitigation of methane emissions from coastal mangrove sediments.

Mangrove forests represent important sources of methane, partly thwarting their ecosystem function as an efficient atmospheric carbon dioxide sink. Many studies have focused on the spatial and temporal variability of methane emissions from mangrove ecosystems, yet little is known about the microbial and physical controls on the release of biogenic methane from tidally influenced mangrove sediments. Here, we show that aerobic methane oxidation is a key microbial process that effectively reduces methane emissions from mangrove sediments. We further demonstrate clear links between the tidal cycle and fluctuations in methane fluxes, with contrasting methane emission rates under different tidal amplitudes. Our data suggest that both the microbial methane oxidation activity and pressure-induced advective transport modulated methane fluxes in the mangrove sediments. Methane oxidation activity is limited by the availability of oxygen in the surface sediments, which in turn is controlled by tidal dynamics, further highlighting the interactive physico-biogeochemical controls on biological methane fluxes. Although we found some molecular evidence for anaerobic methanotrophs in the deeper sediments, anaerobic methane oxidation seems to play only a minor role in the mangrove sediments, with potential rates being two orders of magnitude lower than those of aerobic methane oxidation. Our findings confirmed the importance of surface sediments as biological barrier for methane. Specifically, when sediments were exposed to the air, methane consumption increased by ∼227%, and the methane flux was reduced by ∼62%, compared to inundated conditions. Our data demonstrate how tides can orchestrate the daily rhythm of methane consumption and production within mangrove sediments, thus explaining the temporal variability of methane emissions in the tidally influenced coastal mangrove systems.

Comparative analysis of size-fractional eukaryotic microbes in subtropical riverine systems inferred from 18S rRNA gene V4 and V9 regions.

Eukaryotic microbes play key ecological roles in riverine ecosystems. Amplicon sequencing has greatly facilitated the identification and characterization of eukaryotic microbial communities. Currently, 18S rRNA gene V4 and V9 hypervariable regions are widely used for sequencing eukaryotic microbes. Identifying optimal regions for the profiling of size-fractional eukaryotic microbial communities is critical for microbial ecological studies. In this study, we spanned three rivers with typical natural-human influenced transition gradients to evaluate the performance of the 18S rRNA gene V4 and V9 hypervariable regions for sequencing size-fractional eukaryotic microbes (>180 µm, 20-180 µm, 5-20 µm, 3-5 µm, 0.8-3 µm). Our comparative analysis revealed that amplicon results depend on the specific species and microbial size. The V9 region was most effective for detecting a broad taxonomic range of species. The V4 region was superior to the V9 region for the identification of microbes in the minor 3 µm and at the family and genus levels, especially for specific microbial groups, such as Labyrinthulomycetes. However, the V9 region was more effective for studies of diverse eukaryotic groups, including Archamoebae, Heterolobosea, and Microsporidia, and various algae, such as Haptophyta, Florideophycidae, and Bangiales. Our results highlight the importance of accounting for potential misclassifications when employing both V4 and V9 regions for the identification of microbial sequences. The use of optimal regions for amplification could enhance the utility of amplicon sequencing in environmental studies. The insights gained from this work will aid future studies that employ amplicon-based identification approaches for the characterization of eukaryotic microbial communities and contribute to our understanding of microbial ecology within aquatic systems.

Exciton Dissociation and Recombination Afford Narrowband Organic Afterglow Through Efficient FRET.

Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge challenge since it is intrinsically contradictory to the triplet- and solid-state emission nature of organic afterglow. Here, narrow-band, long-lived, and full-color organic LPL is realized by isolating multi-resonant thermally activated delayed fluorescent (MR-TADF) fluorophores in a glassy steroid-type host through a facile melt-cooling treatment. Such prepared host becomes capable of exciton dissociation and recombination (EDR) upon photoirradiation for both long-lived fluorescence and phosphorescence; and, the efficient Förster resonance energy transfer (FRET) from the host to various MR-TADF emitters leads to high-performance LPL, exhibiting small FWHM of 33 nm, long persistent time over 10 s, and facile color-tuning in a wide range from deep-blue to orange (414-600 nm). Moreover, with the extraordinary narrowband LPL and easy processability of the material, centimeter-scale flexible optical waveguide fibers and integrated FWHM/color/lifetime-resolved multilevel encryption/decryption devices have been designed and fabricated. This novel EDR and singlet/triplet-to-singlet FRET strategy to achieve excellent LPL performances illustrates a promising way for constructing flexible organic afterglow with easy preparation methods, shedding valuable scientific insights into the design of narrow-band emission in organic afterglow.

Hybrid Local and Charge-Transfer Material with Ultralong Room Temperature Phosphorescence for Efficient Organic Afterglow Light-Emitting Diodes.

Organic ultralong room temperature phosphorescence (OURTP) materials capable of combining various emission behaviors for diversified optoelectronic properties and applications have recently gained a vigorous development, but it remains a forbidden challenge in designing OURTP molecules with hybrid local and charge-transfer (HLCT) feature, possibly due to the elevated difficulties in simultaneously meeting the stringent requirements of both HLCT and OURTP emitters. Here, through introducing multiple heteroatoms into one-dimensional fused ring of coumarin with moderate charge transfer perturbation in donor-π-acceptor architecture, we demonstrate a HLCT-featured OURTP molecule showing both promoted fluorescence with a quantum yield of 77 % in solution and long-lived OURTP with a lifetime of 251 ms in conventional host material used in electroluminescent device. Thus, efficient OURTP organic light-emitting diodes (OLEDs) were fabricated, exhibiting bright electroluminescence with an exciton utilization efficiency of 85 % and yellow OURTP lasting over 2 s for afterglow. Impressively, the HLCT OURTP-OLEDs can be further optimized to reach an unprecedented total external quantum efficiency (EQE) of ~12 % and OURTP EQE up to 3.11 %, representing the highest performance among the reported OURTP-OLEDs. These impressive results highlight the significance to fuse HLCT and OURTP together in enriching OURTP materials and improving the afterglow OLED performances.

Network pharmacology-based investigation of the effects of Shenqi Fuzheng injection on glioma proliferation and migration via the SRC/PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In the clinic, Shenqi Fuzheng Injection (SFI) is used as an adjuvant for cancer chemotherapy. However, the molecular mechanism is unclear. AIM OF THE STUDY: We screened potential targets of SFI action on gliomas by network pharmacology and performed experiments to validate possible molecular mechanisms against gliomas. MATERIALS AND METHODS: We consulted relevant reports on the SFI and glioma incidence from PubMed and Web of Science and focused on the mechanism through which the SFI inhibits glioma. According to the literature, two primary SFI components-Codonopsis pilosula (Franch.) Nannf. and Astragalus membranaceus (Fisch.) Bunge-have been found. All plant names have been sourced from "The Plant List" (www.theplantlist.org). The cell lines U87, T98G and GL261 were used in this study. The inhibitory effects of SFI on glioma cells U87 and T98G were detected by CCK-8 assay, EdU, plate cloning assay, scratch assay, Transwell assay, immunofluorescence, flow cytometry and Western blot. A subcutaneous tumor model of C57BL/6 mice was constructed using GL261 cells, and the SFI was evaluated by HE staining and immunohistochemistry. The targets of glioma and the SFI were screened using network pharmacology. RESULTS: A total of 110 targets were enriched, and a total of 26 major active components in the SFI were investigated. There were a total of 3,343 targets for gliomas, of which 79 targets were shared between the SFI and glioma tissues. SFI successfully prevented proliferation and caused cellular S-phase blockage in U87 and T98G cells, thus decreasing their growth. Furthermore, SFI suppressed cell migration by downregulating EMT marker expression. According to the results of the in vivo tests, the SFI dramatically decreased the development of tumors in a transplanted tumour model. Network pharmacological studies revealed that the SRC/PI3K/AKT signaling pathway may be the pathway through which SFI exerts its anti-glioma effects. CONCLUSIONS: The findings revealed that the SRC/PI3K/AKT signaling pathway may be involved in the mechanism through which SFI inhibits the proliferation and migration of glioma cells.

Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.

The metastasis is a multistep process in which a small proportion of cancer cells are detached from the colony to enter into blood cells for obtaining a new place for metastasis and proliferation. The metastasis and cell plasticity are considered major causes of cancer-related deaths since they improve the malignancy of cancer cells and provide poor prognosis for patients. Furthermore, enhancement in the aggressiveness of cancer cells has been related to the development of drug resistance. Metastasis of pancreatic cancer (PC) cells has been considered one of the major causes of death in patients and their undesirable prognosis. PC is among the most malignant tumors of the gastrointestinal tract and in addition to lifestyle, smoking, and other factors, genomic changes play a key role in its progression. The stimulation of EMT in PC cells occurs as a result of changes in molecular interaction, and in addition to increasing metastasis, EMT participates in the development of chemoresistance. The epithelial, mesenchymal, and acinar cell plasticity can occur and determines the progression of PC. The major molecular pathways including STAT3, PTEN, PI3K/Akt, and Wnt participate in regulating the metastasis of PC cells. The communication in tumor microenvironment can provide by exosomes in determining PC metastasis. The components of tumor microenvironment including macrophages, neutrophils, and cancer-associated fibroblasts can modulate PC progression and the response of cancer cells to chemotherapy.

Transcriptomics and molecular docking reveal the potential mechanism of lycorine against pancreatic cancer.

BACKGROUND: Pancreatic cancer is an extremely malignant digestive tumor, however, owing to its high drug resistance of pancreatic cancer, the search for more effective anti-pancreatic cancer drugs is urgently needed. Lycorine, an alkaloid of natural plant origin, exerts antitumor effects on a variety of tumors. PURPOSE: This study aimed to investigate the therapeutic effect of lycorine on pancreatic cancer and elucidate its potential molecular mechanism. METHODS: Two pancreatic cancer cell lines, PANC-1 and BxPC-3, were used to investigate the therapeutic effects of lycorine on pancreatic cancer in vitro using the CCK8 assay, colony formation assay, 5-Ethynyl-2'- deoxyuridine (EdU) incorporation assay, flow cytometry, and western blotting. Transcriptome sequencing and gene set enrichment analysis (GSEA) were used to analyze the differentially expressed genes and pathways after lycorine treatment. Molecular docking, quantitative real-time PCR (qRT-PCR), oil red O staining, small interfering RNA (siRNA) transfection, and other experiments were performed to further validate the differentially expressed genes and pathways. In vivo experiments were conducted to investigate lycorine's inhibitory effects and toxicity on pancreatic cancer using a tumor-bearing mouse model. RESULTS: Lycorine inhibited the proliferation of pancreatic cancer cells, caused G2/M phase cycle arrest and induced apoptosis. Transcriptome sequencing and GSEA showed that lycorine inhibition of pancreatic cancer was associated with fatty acid metabolism, and aldehyde dehydrogenase 3A1 (ALDH3A1) was a significantly enriched target in the fatty acid metabolism process. ALDH3A1 expression was significantly upregulated in pancreatic cancer and was closely associated with prognosis. Molecular docking showed that lycorine binds strongly to ALDH3A1. Further studies revealed that lycorine inhibited the fatty acid oxidation (FAO) process in pancreatic cancer cells and induced cell growth inhibition and apoptosis through ALDH3A1. Lycorine also showed significant suppressive effects in tumor-bearing mice. Importantly, it did not result in significant toxicity to liver and kidney of mice, demonstrating its therapeutic potential as a safe antitumor agent. CONCLUSION: Lycorine inhibited pancreatic cancer cell proliferation, blocked the cell cycle, and induced apoptosis by targeting ALDH3A1. FAO inhibition was identified for the first time as a possible mechanism for the anticancer effects of lycorine. These findings enrich the theory of targeted therapy for pancreatic cancer, expand our understanding of the pharmacological targets of lycorine, and provide a reference for exploring its natural components.

High-Quality Circularly Polarized Organic Afterglow from Nonconjugated Amorphous Chiral Copolymers.

Organic materials featuring circularly polarized luminescence (CPL) and/or afterglow emission represent an active research frontier with promising applications in various fields, but the achievement of high-performance CPL organic afterglow (CPOA) remains a huge challenge due to the intrinsic contradictions between the luminescent lifetime/dissymmetry factor (glum) and phosphorescent quantum efficiency (PhQY). Herein, we report a simple and universal approach to design efficient CPOA from amorphous copolymers by incorporating chiral chromophores into a nonconjugated clusterization-triggered emissive polymer with plenty of hydron-bonding interactions, followed by aggregation engineering using water dissolution and evaporation. With this chiral copolymerization and aggregation engineering (CCAE) strategy, high-performance CPOA polymers with PhQYs of up to 6.32%, ultralong lifetimes of over 650 ms, glum values of 3.54 × 10-3, and the highest figure-of-merit were achieved at room temperature. Given the impressive CPOA performance of these polymers, the applications in multilevel data anticounterfeiting and reversible displays with high stability were demonstrated. These findings through the CCAE strategy to overcome the inherent restraints of CPOA materials lay the foundation for the development of amorphous polymers with superior CPOA, significantly expanding the understanding of CPL and the design of organic afterglow materials.

Expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma.

Objective: To investigate the expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma and adjacent tissues. Methods: The expression of COX-2 and NUCB1 and their effects on prognosis were predicted using bioinformatics. Immunohistochemistry was used to identify the expression of two molecules in 56 cases of colorectal adenocarcinoma and the surrounding tissues. The expression of two molecules and their association with clinicopathological variables were examined using the chi-square test. The association between COX-2 and NUCB1 was investigated using the Spearman correlation test. Results: The STRING database revealed that COX-2 and NUCB1 were strongly linked. According to the UALCAN and HPA database, COX-2 was upregulated while NUCB1 was downregulated in colorectal adenocarcinoma, both at the protein and gene levels. The OS times for COX-2 and NUCB1 high expression, however, exhibited the same patterns. The rate of positive COX-2 immunohistochemical staining in cancer tissues was 69.64% (39/56), which was significantly higher than the rate in healthy tissues 28.57% (16/56). NUCB1 was expressed positively in cancer tissues at a rate of 64.29% (36/56) compared to just 19.64% (11/56) in neighboring tissues. The positive expression levels of COX-2 and NUCB1 were both closely related to clinical stage, differentiation degree, and lymphatic metastases (P < 0.05). In colorectal cancer, COX-2 and NUCB1 expression were significantly correlated (rs = 0.6312, P < 0.001). Conclusion: Both COX-2 and NUCB1 are overexpressed and significantly associated in colorectal adenocarcinoma.

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca 2+ overload and the TGF-ß1/Smad signaling pathway.

The inwardly rectifying potassium channel Kir2.1 is closely associated with many cardiovascular diseases. However, the effect and mechanism of Kir2.1 in diabetic cardiomyopathy remain unclear. In vivo, we use STZ to establish the model, and ventricular structural changes, myocardial inflammatory infiltration, and myocardial fibrosis severity are detected by echocardiography, histological staining, immunohistochemistry, and western blot analysis, respectively. In vitro, a myocardial fibrosis model is established with high glucose. The Kir2.1 current amplitude, intracellular calcium concentration, fibrosis-related proteins, and TGF-ß1/Smad pathway proteins are detected by whole-cell patch clamp, calcium probes, western blot analysis, and immunofluorescence, respectively. The in vivo results show that compared to diabetic cardiomyopathy, zacopride (a Kir2.1 selective agonist) significantly reduces the left ventricular systolic diameter and diastolic diameter, increases the left ventricular ejection fraction and left ventricular short-axis shortening, improves the degree of cell necrosis, and reduces the expression of myocardial interstitial fibrosis protein and collagen fibre deposition area. The in vitro results show that the current amplitude and protein expression of Kir2.1 are both decreased in the high glucose-induced myocardial fibrosis model. Additionally, zacopride significantly upregulates the expression of Kir2.1 and inhibits the expressions of the fibrosis-related proteins α-SMA, collagen I, and collagen III. Activation of Kir2.1 reduces the intracellular calcium concentration and inhibits the protein expressions of TGF-ß1 and p-Smad 2/3. Activation of Kir2.1 can improve myocardial fibrosis induced by diabetic cardiomyopathy, and the possible mechanism may be related to inhibiting Ca 2+ overload and the TGF-ß1/Smad signaling pathway.

Variation of glomalin-metal binding capacity in 1 m soil profiles from mangrove forests to mudflat and affected factor analysis.

Glomalin-related soil protein (GRSP) plays an important role in soil metal sequestration in coastal wetlands. Additionally, it can release dissolved organic matter (GDOM) in water-soaked condition. The purpose of this study was to clarify the variation of GRSP's heavy metal immobilisation capacity at soil profiles of coastal wetland, and explore the compositional characteristics of GDOM and its influence on the heavy metals' environmental behaviour. The results indicated that the metal immobilisation capacity of GRSP decreased with increasing burial depth. The contributions of GRSP to soil Cr, As, and Pb were higher in both mangrove soils (K. obovata and A. marina forests) than in the mudflat. Oxygen-containing functional groups of GRSP (CO, -COO-, etc.) played a positive role in heavy metals accumulation. Redundancy analysis (RDA) showed that high soil pH was not conducive to the enrichment of heavy metals by GRSP. Besides, the concentrations of GRSP-Fe showed a significant positive correlation with the concentrations of other metals (Cu, As, and Pb) in GRSP. It is speculated that the Fe minerals in GRSP contributed the enrichment of heavy metals. Based on PARAFAC modelling, four fluorescent components of GDOM were identified, including three humic-like fluorescent components and one tyrosine-like fluorescent component. The contributions of GDOM to GRSP-bound heavy metals fluctuated between 4.05 % and 88.80 %, which could enhance the fluidity of heavy metals in water and weaken the soil heavy metal immobilisation capacity of GRSP. High salinity exerted an inhibitory effect on the heavy metal content of the GDOM. This study comprehensively explored the potential of GRSP to immobilise heavy metals in wetland soils and highlighted the potential heavy metal risks associated with the GDOM component in water, which could contribute to the multidimensional assessment and control of heavy metal pollution in coastal wetlands.

Anxiety and depression in lung cancer: effect of psychological interventions - network meta-analysis.

BACKGROUND: The prevalence of depression and anxiety is high in patients with lung cancer, while multiple psychological interventions have revealed a positive impact on patients' negative emotions. However, it remains scarce which psychological intervention is the best choice for patients.This study was conducted to compare and rank the efficacy of psychological interventions on anxiety and depression in patients with lung cancer using a network meta-analysis. METHODS: The Chinese academic database (CNKI, Wan Fang and Vip) and English academic database (The Cochrane Library, PubMed, PsycINFO and Web of Science) were searched from their inception to March 2022. Randomised controlled studies of psychological interventions on depression and anxiety in patients with lung cancer were included. Study selection and evaluation were conducted independently by two researchers. Included studies were performed a network meta-analysis to compare and rank the psychological interventions for negative emotions of patients with lung cancer. The clustered ranking of psychotherapies in the network was based on surface under the cumulative probability ranking curve values. RESULTS: 23 studies (2221 participants) with 13 psychological interventions were retrieved. The random-effects model showed a significantly large effect size of supportive therapy for anxiety (mean difference, MD 14.38, 95% CI 2.42 to 26.21) and depression (MD 14.29, 95% CI 2.74 to 25.70). The supportive therapy, sandplay therapy and music therapy were top three rankings of interventions for anxiety, while supportive therapy, dignity therapy and sandplay therapy were the top three interventions for depression. CONCLUSIONS: Supportive therapy would be a more appropriate option for alleviating negative emotions in patients with lung cancer. Other psychological intervention techniques may be used as alternatives, such as sandplay therapy and music therapy for anxiety, dignity therapy and sandplay therapy for depression. PROSPERO REGISTRATION NUMBER: CRD42022320188.

Biphasic effects of statins on neuron cell functions under oxygen-glucose deprivation and normal culturing conditions via different mechanisms.

While there is a growing interest in the use of statins, HMG-CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury-induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation-independent manner. Other mechanisms are involved in the pro-apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS.

Lactate: The Mediator of Metabolism and Immunosuppression.

The Warburg effect, one of the hallmarks of tumors, produces large amounts of lactate and generates an acidic tumor microenvironment via using glucose for glycolysis. As a metabolite, lactate not only serves as a substrate to provide energy for supporting cell growth and development but also acts as an important signal molecule to affect the biochemical functions of intracellular proteins and regulate the biological functions of different kinds of cells. Notably, histone lysine lactylation (Kla) is identified as a novel post-modification and carcinogenic signal, which provides the promising and potential therapeutic targets for tumors. Therefore, the metabolism and functional mechanism of lactate are becoming one of the hot fields in tumor research. Here, we review the production of lactate and its regulation on immunosuppressive cells, as well as the important role of Kla in hepatocellular carcinoma. Lactate and Kla supplement the knowledge gap in oncology and pave the way for exploring the mechanism of oncogenesis and therapeutic targets. Research is still needed in this field.

Association of mental health with clinical outcomes in hospitalized patients with moderate COVID-19.

OBJECTIVE: To assess the association of depression and anxiety with clinical outcomes and laboratory markers among hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: A prospective cohort study in Wuhan, China was conducted in 205 adult hospitalized patients with a diagnosis of moderate coronavirus disease from admission through discharge or death. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The primary outcome was the incidence of severe or critical COVID-19, and the secondary outcomes were increased length of hospital stay and altered laboratory markers during follow up. RESULTS: Among the 205 hospitalized patients (mean age 58 years; 51.7% male), 25 (12.2%) developed severe or critical COVID-19. According to the HADS scores, 51 (24.9%) and 92 (44.9%) of participants presented with clinically significant anxiety and depression, respectively. Using multi-variable adjusted Cox regression analysis, the adjusted hazard ratio of developing severe or critical COVID-19 associated with anxiety and depression was 1.55 (95% CI: 0.63, 3.80) and 4.28 (95% CI: 1.20, 15.30), respectively. The risk of developing severe or critical COVID-19 with both anxiety and depression was more than four times higher than in patients without anxiety or depression (HR, 4.05; 95% CI: 1.02, 16.00). In addition, both the trends of depression and anxiety were positively associated with a prolonged duration of hospitalization, and immune response was significantly decreased in patients with depression than those without. CONCLUSIONS: In patients having coronavirus disease, depression was associated with worse clinical outcomes. These findings highlight the importance of prevention and management of mental health problems in confronting the COVID-19 pandemic.

Spatial heterogeneity in chemical composition and stability of glomalin-related soil protein in the coastal wetlands.

GRSP is widely distributed in coastal wetlands, and there is a tendency for it to degrade with increasing burial depth. However, the dynamic changes in the chemical composition and stability of GRSP during the burial process are still unclear. The purpose of this study is to clarify the chemical composition and accumulation characteristics of GRSP during the burial process in the Zhangjiang estuary. In a field study, soil cores to the depth of 100 cm were collected in the estuary from mangrove forests dominated by Kandelia obovata and Avicennia marina, and from mudflat. The results showed that the concentration of GRSP in mangrove forest soil was significantly higher than that in the mudflat (p < 0.05), and the C/N ratio of GRSP increased with depth at all sites. Analysis of Fourier transform infrared (FTIR) data showed that the degradation rates of the GRSP's compositions varied with increasing burial depth, with microbial action and pH possibly being the main factors affecting degradation. Values of recalcitrance index (RI) showed that the stability of GRSP increased with increasing depth, and the contribution of GRSP to soil organic carbon (SOC) also increased. This suggests that the burial process plays a role in screening and storing the stable components of GRSP. Overall, our findings suggest that the concentration and chemical composition of GRSP vary dynamically according to habitat and burial processes. In addition, the improved stability of GRSP could contribute to carbon sequestration in coastal wetlands.