Histone variant H2A.Z is required for plant salt response by regulating gene transcription.

As a well-conserved histone variant, H2A.Z epigenetically regulates plant growth and development as well as the interaction with environmental factors. However, the role of H2A.Z in response to salt stress remains unclear, and whether nucleosomal H2A.Z occupancy work on the gene responsiveness upon salinity is obscure. Here, we elucidate the involvement of H2A.Z in salt response by analysing H2A.Z disorder plants with impaired or overloaded H2A.Z deposition. The salt tolerance is dramatically accompanied by H2A.Z deficiency and reacquired in H2A.Z OE lines. H2A.Z disorder changes the expression profiles of large-scale of salt responsive genes, announcing that H2A.Z is required for plant salt response. Genome-wide H2A.Z mapping shows that H2A.Z level is induced by salt condition across promoter, transcriptional start site (TSS) and transcription ending sites (-1 kb to +1 kb), the peaks preferentially enrich at promoter regions near TSS. We further show that H2A.Z deposition within TSS provides a direct role on transcriptional control, which has both repressive and activating effects, while it is found generally H2A.Z enrichment negatively correlate with gene expression level response to salt stress. This study shed light on the H2A.Z function in salt tolerance, highlighting the complex regulatory mechanisms of H2A.Z on transcriptional activity for yielding appropriate responses to particularly environmental stress.

Asymmetrical disassortative pollination mediated by long-/short-tongued pollinators in a distylous Limonium myrianthum (Plumbaginaceae) with a short corolla tubular small flower.

In heterostylous plants, short-tongued pollinators are often ineffective/inefficient owing to the limitations imposed by a long corolla tube. However, it is unclear how disassortative pollen transfer is achieved in small flowers. We investigated the pollination pattern and floral morph variation by analyzing heterostylous syndrome, pollinator groups, and pollen deposition after a single visitation in two Limonium myrianthum populations with short-corolla-tubular small flowers. The predominant pollinators in the Hutubi population were pollen-seeking short-tongued syrphids, which can only transfer pollen between high-level sexual organs. In the Xishan population, nectar-seeking short-tongued insects were efficient pollinators with symmetrical disassortative pollen transfer between high- and low-level sexual organs, whereas long-tongued pollinators had a low efficiency between high-level sexual organs due to the low contact probability with the stigma of long-styled flowers (L-morph), which no longer offered the same advantage observed in tubular flowers. Asymmetrical disassortative pollination may cause the female fitness of short-styled (S-morph) individuals in the Hutubi and L-morph individuals in the Xishan population to suffer greater selection pressure and exhibit a higher degree of floral morph variation. Limonium myrianthum exhibits an unusual pollination pattern in which the small flowers with short corolla tubes make it possible for short-tongued insects to become effective pollinators. However, factors such as the position of stigma-anther within the flower, pollinator species and their preference further caused asymmetrical disassortative pollen transfer. Therefore, more factors should be considered when evaluating the effectiveness of short- and long-tongued insects in pollination service.

Floral morph variation mediated by clonal growth and pollinator functional groups of Limonium otolepis in a heterostylous fragmented population.

Abstract. Heterostyly, a genetic style polymorphism, is linked to symmetric pollen transfer, vital for its maintenance. Clonal growth typically impacts sexual reproduction by influencing pollen transfer. However, the floral morph variation remains poorly understood under the combined effects of pollinators and clonal growth in heterostyly characterized by negative frequency-dependent selection and disassortative mating. We estimated morph ratios, ramets per genet and heterostylous syndrome and quantified legitimate pollen transfer via clonal growth, pollinators and reciprocal herkogamy between floral morphs in Limonium otolepis, a fragmented population composed of five subpopulations in the desert environment of northwestern China, with small flower and large floral morph variation. All subpopulations but one exhibited pollen-stigma morphology dimorphism. The compatibility between mating types with different pollen-stigma morphologies remained consistent regardless of reciprocal herkogamy. Biased ratios and ramets per genet of the two mating types with distinct pollen-stigma morphologies caused asymmetric pollen flow and varying fruit sets in all subpopulations. Short-tongued insects were the primary pollinators due to small flower sizes. However, pollen-feeding Syrphidae sp. triggered asymmetry in pollen flow between high and low sex organs, with short-styled morphs having lower stigma pollen depositions and greater variation. Clonal growth amplified this variation by reducing intermorph pollen transfer. All in all, pollinators and clonal growth jointly drive floral morph variation. H-morphs with the same stigma-anther position and self-incompatibility, which mitigate the disadvantages of sunken low sex organs with differing from the classical homostyly, might arise from long- and short-styled morphs through a 'relaxed selection'. This study is the first to uncover the occurrence of the H-morph and its associated influencing factors in a distylous plant featuring clonal growth, small flowers and a fragmented population.

Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis.

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.

Directionally Illuminated Autostereoscopy with Seamless Viewpoints for Multi-Viewers.

Autostereoscopy is usually perceived at finite viewpoints that result from the separated pixel array of a display system. With directionally illuminated autostereoscopy, the separation of the illumination channel from the image channel provides extra flexibility in optimizing the performance of autostereoscopy. This work demonstrates that by taking advantage of illumination freedom, seamless viewpoints in the sweet viewing region, where the ghosting does not cause significant discomfort, are realized. This realization is based on illuminating the screen with a polyline array of light emitting diodes (LEDs), and continuous viewpoints are generated through independent variation in the radiance of each individual LED column. This new method is implemented in the directionally illuminated display for both single and multiple viewers, proving its effectiveness as a valuable technique for achieving a high-quality and high-resolution autostereoscopic display with seamless viewpoints.

Endogenous melatonin involved in plant salt response by impacting auxin signaling.

KEY MESSAGE: The study on melatonin biosynthesis mutant snat1snat2 revealed that endogenous melatonin plays an important role in salt responsiveness by mediating auxin signaling. Melatonin is a pleiotropic signaling molecule, which, besides being involved in multiple growth and developmental processes, also mediates environmental stress responses. However, whether and how endogenous melatonin is involved in salt response has not been determined. In this study, we elucidated the involvement of endogenous melatonin in salt response by investigatiing the impact of salt stress on a double mutant of Arabidopsis (snat1snat2) defective in melatonin biosynthesis genes SNAT1 and SNAT2. This mutant was found to exhibit salt sensitivity, manifested by unhealthy growth, ion imbalance and ROS accumulation under salt stress. Transcriptomic profiles of snat1snat2 revealed that the expression of a large number of salt-responsive genes was affected by SNAT defect, and these genes were closely related to the synthesis of auxin and several signaling pathways. In addition, the salt-sensitive growth phenotype of snat1snat2 was alleviated by the application of exogenous auxin. Our results show that endogenous melatonin may be essential for plant salt tolerance, a function that could be correlated with diverse activity in mediating auxin signaling.

Ablation of Shank1 Protects against 6-OHDA-induced Cytotoxicity via PRDX3-mediated Inhibition of ER Stress in SN4741 Cells.

BACKGROUND: Postsynaptic density (PSD) is an electron-dense structure that contains various scaffolding and signaling proteins. Shank1 is a master regulator of the synaptic scaffold located at glutamatergic synapses, and has been proposed to be involved in multiple neurological disorders. METHODS: In this study, we investigated the role of shank1 in an in vitro Parkinson's disease (PD) model mimicked by 6-OHDA treatment in neuronal SN4741 cells. The expression of related molecules was detected by western blot and immunostaining. RESULTS: We found that 6-OHDA significantly increased the mRNA and protein levels of shank1 in SN4741 cells, but the subcellular distribution was not altered. Knockdown of shank1 via small interfering RNA (siRNA) protected against 6-OHDA treatment, as evidenced by reduced lactate dehydrogenase (LDH) release and decreased apoptosis. The results of RT-PCR and western blot showed that knockdown of shank1 markedly inhibited the activation of endoplasmic reticulum (ER) stress associated factors after 6-OHDA exposure. In addition, the downregulation of shank1 obviously increased the expression of PRDX3, which was accompanied by the preservation of mitochondrial function. Mechanically, downregulation of PRDX3 via siRNA partially prevented the shank1 knockdowninduced protection against 6-OHDA in SN4741 cells. CONCLUSION: In summary, the present study has provided the first evidence that the knockdown of shank1 protects against 6-OHDA-induced ER stress and mitochondrial dysfunction through activating the PRDX3 pathway.

Cobalt doping amount determines dominant reactive species in peroxymonosulfate activation via porous carbon catalysts co-doped by cobalt and nitrogen.

Switching the reaction routes in peroxymonosulfate (PMS)-based advanced oxidation processes have attracted much attention but remain challenging. Herein, a series of Co-N/C catalysts with different compositions and structures were prepared by using bimetallic zeolitic imidazolate frameworks based on ZIF-8 and ZIF-67 (xZn/Co-ZIFs). Results show that Co doping amount could mediate the transformation of the activation pathway of PMS over Co-N/C. When Co doping amount was less than 10%, the constructed xCo-N/C/PMS system (x ≤ 10%) was singlet oxygen-dominated reaction; however further increasing Co doping amount would lead to the generation and coexistence of sulfate radicals and high-valent cobalt, besides singlet oxygen. Furthermore, the nitrogen-coordinated Co (Co-NX) sites could serve as main catalytically active sites to generate singlet oxygen. While excess Co doping amount caused the formation of Co nanoparticles from which leached Co ions were responsible for the generation of sulfate radicals and high-valent cobalt. Compared to undoped N/C, Co doping could significantly enhance the catalytic performance. The 0.5% Co-N/C could achieve the optimum degradation (0.488 min-1) and mineralization abilities (78.4%) of sulfamethoxazole among the investigated Co-N/C catalysts, which was superior to most of previously reported catalysts. In addition, the application prospects of the two systems in different environmental scenarios (pH, inorganic anions and natural organic matter) were assessed and showed different degradation behaviors. This study provides a strategy to regulate the reactive species in PMS-based advanced oxidation process.

Arabidopsis nucleoporin NUP96 mediates plant salt tolerance by modulating the transcription of salt-responsive genes.

MAIN CONCLUSION: Physiological and molecular tests show that NUP96 plays an important role in the plant response to salt stress, resulting from the reprogramming of transcriptomic profiles, which are likely to be mediated by the influence on the nuclear/cytosol shuttling of the key regulators of salt tolerance. As a key component of the nuclear pore complex (NPC), nucleoporin 96 (NUP96) is critical for modulating plant development and interactions with environmental factors, but whether NUP96 is involved in the salt response is still unknown. Here, we analyzed the role of Arabidopsis NUP96 under salt stress. The loss-of-function mutant nup96 exhibited salt sensitivity in terms of rosette growth and root elongation, and showed attenuated capacity in maintaining ion and ROS homeostasis, which could be compensated for by the overexpression of NUP96. RNA sequencing revealed that many salt-responsive genes were misregulated after NUP96 mutation, and especially NUP96 is required for the expression of a large portion of salt-induced genes. This is likely correlated with the activity in facilitating nuclear/cytosol transport of the underlying regulators in salt tolerance such as the transcription factor ATAP2, targeted by eight downregulated genes in nup96 under salt stress. Our results illustrate that NUP96 plays an important role in the salt response, probably by regulating the nucleocytoplasmic shuttling of key mRNAs or proteins associated with plant salt responsiveness.

Biochar addition accelerates the humification process by affecting the microbial community during human excreta composting.

Biochar addition plays an important role in manure composting, but its driving mechanism on microbial succession and humification process of human excreta composting is still unclear. In the present study, the mechanism of biochar addition was explored by analysing the humification process and microbial succession pattern of human excreta aerobic composting without and with 10% biochar (HF and BHF). Results indicated that BHF improved composting temperature, advanced the thermophilic phase by 1 d, increased the germination index by 49.03%, promoted the growth rate of humic acid content by 17.46%, and raised the compost product with the ratio of humic acid to fulvic acid (HA/FA) by 16.19%. Biochar regulated the diversity of fungi and bacteria, increasing the relative abundance of Planifilum, Meyerozyma and Melanocarpus in the thermophilic phase, and Saccharomonospora, Flavobacterium, Thermomyces and Remersonia in the mature phase, which accelerates the humification. Bacterial communities' succession had an obvious correlation with the total carbon, total nitrogen, and temperature (P < 0.05), while the succession of fungal communities was influenced by the HA/FA and pH (P < 0.05). This study could provide a reference for the improvement of on-site human excreta harmless by extending the thermophilic phase, and facilitating the humification in human excreta compost with biochar addition.

Characterizations of the multi-kingdom gut microbiota in Chinese patients with gouty arthritis.

OBJECTIVE: The gut microbial composition has been linked to metabolic and autoimmune diseases, including arthritis. However, there is a dearth of knowledge on the gut bacteriome, mycobiome, and virome in patients with gouty arthritis (GA). METHODS: We conducted a comprehensive analysis of the multi-kingdom gut microbiome of 26 GA patients and 28 healthy controls, using whole-metagenome shotgun sequencing of their stool samples. RESULTS: Profound alterations were observed in the gut bacteriome, mycobiome, and virome of GA patients. We identified 1,117 differentially abundant bacterial species, 23 fungal species, and 4,115 viral operational taxonomic units (vOTUs). GA-enriched bacteria included Escherichia coli_D GENOME144544, Bifidobacterium infantis GENOME095938, Blautia_A wexlerae GENOME096067, and Klebsiella pneumoniae GENOME147598, while control-enriched bacteria comprised Faecalibacterium prausnitzii_G GENOME147678, Agathobacter rectalis GENOME143712, and Bacteroides_A plebeius_A GENOME239725. GA-enriched fungi included opportunistic pathogens like Cryptococcus neoformans GCA_011057565, Candida parapsilosis GCA_000182765, and Malassezia spp., while control-enriched fungi featured several Hortaea werneckii subclades and Aspergillus fumigatus GCA_000002655. GA-enriched vOTUs mainly attributed to Siphoviridae, Myoviridae, Podoviridae, and Microviridae, whereas control-enriched vOTUs spanned 13 families, including Siphoviridae, Myoviridae, Podoviridae, Quimbyviridae, Phycodnaviridae, and crAss-like. A co-abundance network revealed intricate interactions among these multi-kingdom signatures, signifying their collective influence on the disease. Furthermore, these microbial signatures demonstrated the potential to effectively discriminate between patients and controls, highlighting their diagnostic utility. CONCLUSIONS: This study yields crucial insights into the characteristics of the GA microbiota that may inform future mechanistic and therapeutic investigations.

Enhancement of sulfur metabolism and antioxidant machinery confers Bacillus sp. Jrh14-10-induced alkaline stress tolerance in plant.

Alkaline stress is a major environmental challenge that restricts plant growth and agricultural productivity worldwide. Plant growth-promoting rhizobacteria (PGPR) can be used to effectively enhance plant abiotic stress in an environment-friendly manner. However, PGPR that can enhance alkalinity tolerance are not well-studied and the mechanisms by which they exert beneficial effects remain elusive. In this study, we isolated Jrh14-10 from the rhizosphere soil of halophyte Halerpestes cymbalaria (Pursh) Green and found that it can produce indole-3-acetic acid (IAA) and siderophore. By 16S rRNA gene sequencing, it was classified as Bacillus licheniformis. Inoculation Arabidopsis seedlings with Jrh14-10 significantly increased the total fresh weight (by 148.1%), primary root elongation (by 1121.7%), and lateral root number (by 108.8%) under alkaline stress. RNA-Seq analysis showed that 3389 genes were up-regulated by inoculation under alkaline stress and they were associated with sulfur metabolism, photosynthetic system, and oxidative stress response. Significantly, the levels of Cys and GSH were increased by 144.3% and 48.7%, respectively, in the inoculation group compared to the control under alkaline stress. Furthermore, Jrh14-10 markedly enhanced the activities of antioxidant enzymes, resulting in lower levels of O2•-, H2O2, and MDA as well as higher levels of Fv/Fm in alkaline-treated seedlings. In summary, Jrh14-10 can improve alkaline stress resistance in seedlings which was accompanied by an increase in sulfur metabolism-mediated GSH synthesis and antioxidant enzyme activities. These results provide a mechanistic understanding of the interactions between a beneficial bacterial strain and plants under alkaline stress.

Directional screening and identification of potential cytotoxic components from Achnatherum inebrians by a combination of surface palsmon resonance and chromatography.

Objective: To establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology. Methods: Under the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man. Results: Eight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC50 = 5.7 µmol/L), human breast cancer cells MCF7 (IC50 = 7.21 µmol/L) and human lung cancer cells HCC827 (IC50 = 0.75 µmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC50 = 1.65 µmol/L). Conclusion: A comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.

Covalent Bonding Enhanced Polypropylene Based T-ZIF-8 Masterbatch with Superior Photocatalytic and Antibacterial Performances.

In order to solve the problem of poor compatibility between modified-ZIF-8 nanoparticles and mask matrix polypropylene (PP) and melt-blown materials, in this work, PP based modified-ZIF-8 antibacterial masterbatch was prepared employing surface modification and torque blending method. IR, SEM, XRD, XPS, DSC results confirm that the antibacterial masterbatch maintains the chemical and crystal structure of modified-ZIF-8 and the thermal stability of PP. Photocatalytic performance indicates that the antibacterial masterbatch basically maintains the photoresponse range of modified-ZIF-8, has narrower band gap and the superior photocatalytic performance than that of modified-ZIF-8. The photocatalytic antibacterial mechanism of ·O2- and h+ as antibacterial active species is revealed according to the energy band structure and free radical capture experiment. The photocatalytic antibacterial activity of the antibacterial masterbatch against Staphylococcus aureus and Escherichia coli under different dosage holds that the relationship between antibacterial rate and antibacterial agent concentration conforms to Beta distribution, demonstrating second-order kinetic behavior. The antibacterial properties reach the maximum when the loading of modified-ZIF-8 is 2% of the total weight of PP and melt-blown materials. S. aureus and E. coli could be completely killed when the simulated sunlight is irradiated for 30 min. These results indicate that PP based modified-ZIF-8 antibacterial masterbatch has potential application in photocatalytic antibacterial masks.

A Dual-Wavelength Phosphorescent Anti-Counterfeiting Copolymer Containing Eu(III) and Tb(III).

The anti-counterfeiting technology of banknotes, bills and negotiable securities is constantly copied, and it is urgent to upgrade its anti-counterfeiting technology. In view of the defect of easy replication of single-wavelength anti-counterfeiting technology, the bonded copolymer PMEuTb was synthesized, employing the technique of first coordination and then polymerization. The molecular structure of copolymer PMEuTb was confirmed by infrared spectrum and UV-vis absorption spectrum. The internal mechanism of negative correlation between initiator concentration and number-average molecular weight Mn of the copolymer was revealed, and the positive correlation between Mn and luminescent behavior of the copolymer was analyzed. The luminescent properties of copolymer PMEuTb with initiator amount of 0.1% were investigated, the copolymer PMEuTb exhibits dual-wavelength emission of green light and red light under the excitation of ultraviolet light at 254 nm and 365 nm. The copolymer has the lifetime of 1.083 ms at 5D4-7F5 transition and 0.665 ms at 5D0-7F2 transition, which belongs to phosphorescent emitting materials. The copolymer remains stable at 240 °C, and variable temperature photoluminescent spectra demonstrate the luminescent intensity remains 85% at 333 K, meeting the requirements of room temperature phosphorescent anti-counterfeiting materials. The luminescent patterns made by standard screen printing display the green and cuticolor logo at 254 nm and 365 nm, respectively, indicating that the bonded phosphors PMEuTb has potential application in phosphorescent anti-counterfeiting.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

Characterizations of the Gut Bacteriome, Mycobiome, and Virome in Patients with Osteoarthritis.

The gut microbiota plays an essential role in the regulation of the immune system and the etiology of human autoimmune diseases. However, a holistic understanding of the gut bacteriome, mycobiome, and virome in patients with osteoarthritis (OA) remains lacking. Here, we explored the gut microbiotas of 44 OA patients and 46 healthy volunteers via deep whole-metagenome shotgun sequencing of their fecal samples. The gut bacteriome and mycobiome were analyzed using a reference-based strategy. Gut viruses were identified from the metagenomic assembled contigs, and the gut virome was profiled based on 6,567 nonredundant viral operational taxonomic units (vOTUs). We revealed that the gut microbiome (including bacteriome, mycobiome, and virome) of OA patients is fundamentally altered, characterized by a panel of 279 differentially abundant bacterial species, 10 fungal species, and 627 vOTUs. The representative OA-enriched bacteria included Anaerostipes hadrus (GENOME147149), Prevotella sp900313215 (GENOME08259), Eubacterium_E hallii (GENOME000299), and Blautia A (GENOME001004), while Bacteroides plebeius A (GENOME239725), Roseburia inulinivorans (GENOME 001770), Dialister sp900343095 (GENOME075103), Phascolarctobacterium faecium (GENOME233517), and several members of Faecalibacterium and Prevotella were depleted in OA patients. Fungi such as Debaryomyces fabryi (GenBank accession no. GCA_003708665), Candida parapsilosis (GCA_000182765), and Apophysomyces trapeziformis (GCA_000696975) were enriched in the OA gut microbiota, and Malassezia restricta (GCA_003290485), Aspergillus fumigatus (GCA_003069565), and Mucor circinelloides (GCA_010203745) were depleted. The OA-depleted viruses spanned Siphoviridae (95 vOTUs), Myoviridae (70 vOTUs), and Microviridae (5 vOTUs), while 30 Siphoviridae vOTUs were enriched in OA patients. Functional analysis of the gut bacteriome and virome also uncovered their functional signatures in relation to OA. Moreover, we demonstrated that the OA-associated gut bacterial and viral signatures are tightly interconnected, suggesting that they may impact disease together. Finally, we showed that the multikingdom signatures are effective in discriminating the OA patients from healthy controls, suggesting the potential of gut microbiota for the prediction of OA and related diseases. Our results delineated the fecal bacteriome, mycobiome, and virome landscapes of the OA microbiota and provided biomarkers that will aid in future mechanistic and clinical intervention studies. IMPORTANCE The gut microbiome of OA patients was completely altered compared to that in healthy individuals, including 279 differentially abundant bacterial species, 10 fungal species and 627 viral operational taxonomic units (vOTUs). Functional analysis of the gut bacteriome and virome also revealed their functional signatures in relation to OA. We found that OA-associated gut bacterial and viral signatures were tightly interconnected, indicating that they may affect the disease together. The OA patients can be discriminated effectively from healthy controls using the multikingdom signatures, suggesting the potential of gut microbiota for the prediction of OA and related diseases.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study.

OBJECTIVE: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL). METHODS: This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded. RESULTS: The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group. CONCLUSIONS: TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Effect of Cellulose Nanofibrils on the Physical Properties and Frost Resistance of Pervious Concrete.

Pervious concrete has good water permeability and, if used in construction, it can alleviate the heat island effect. However, its low strength and poor durability are major obstacles to its use. This study shows that nano-reinforced pervious concrete created by incorporating cellulose nanofibrils (CNFs) can improve the physical properties and increase the durability of pervious concrete. CNFs were added to the concrete mix in proportions ranging from 0.05% to 0.2% by weight of binder. The additions were found to alter matrix rheology. The hydration kinetics of matrix with differing CNF contents were compared and analyzed. The experimental results show the addition of CNFs delayed peak heat flow and maximum cumulative heat. The 28 d compressive strength of pervious concrete increased by up to 26.5% and 28 d flexural strength by up to 25.8% with the addition of 0.05-0.2% CNFs. Addition of 0.1% and 0.2% CNFs increased water permeability. Addition of 0.05-0.15% CNFs decreased mass loss by 73.2-83.7% after 150 freeze-thaw cycles, which corresponded to an increase in frost resistance. Denser matrices and stronger interfacial transition zones were observed using scanning electron microscopy when 0.05-0.2% CNFs were added.