Mechanistic Investigation into Chemiluminescence from 1,4-Benzoquinone.

Tetrahalogen-1,4-benzoquinone (THBQ) represents a category of H2O2-dependent substrates for chemiluminescence (CL), including tetrafluoro-, tetrachloro-, tetrabromo-, and tetraiodo-1,4-benzoquinone (TFBQ, TCBQ, TBBQ, and TIBQ). A deep understanding of the CL mechanism of THBQ is essential for all H2O2-dependent CL and even some bioluminescence. This article systematically investigates the CL process of THBQ by density functional theory and multireference state theory. The theoretical results confirm the generality of the CL mechanism previously proposed in studies on TCBQ and TBBQ. The dissociation steps producing the emitter of light from dihalogenquinone dioxetane (DHD) and its anion (DHD-), formed by the oxidation of THBQ, were carefully considered. Findings show that the dissociation of DHD/DHD- follows the entropy trap/gradually reversible charge-transfer-induced luminescence (GRCTIL) mechanisms. The dissociation of DHD- is kinetically more advantageous compared with that of DHD. At the practical experimental pH value, the decrease in the electron-withdrawing inductive effect from F to I substituents results in the decrease in the proportions of easily dissociated DHD-, and the increase in the heavy-atom effect from F to I substituents leads to the increase in the phosphorescence emission. These combined factors successively decrease the CL intensity from TFBQ to TCBQ, TBBQ, and TIBQ. The conclusions are verified by the previous experiments on TCBQ and TBBQ, and they are expected to be confirmed by future experiments on TFBQ and TIBQ.

Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.

Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area.

Evolutionarily conserved 12-oxophytodienoate reductase trans-lncRNA pair affects disease resistance in tea (Camellia sinensis) via the jasmonic acid signaling pathway.

Long non-coding RNAs (lncRNAs) have gathered significant attention due to their pivotal role in plant growth, development, and biotic and abiotic stress resistance. Despite this, there is still little understanding regarding the functions of lncRNA in these domains in the tea plant (Camellia sinensis), mainly attributable to the insufficiencies in gene manipulation techniques for tea plants. In this study, we designed a novel strategy to identify evolutionarily conserved trans-lncRNA (ECT-lncRNA) pairs in plants. We used highly consistent base sequences in the exon-overlapping region between trans-lncRNAs and their target gene transcripts. Based on this method, we successfully screened 24 ECT-lncRNA pairs from at least two or more plant species. In tea, as observed in model plants such as Arabidopsis, alfalfa, potatoes, and rice, there exists a trans-lncRNA capable of forming an ECT-lncRNA pair with transcripts of the 12-oxophytodienoate reductase (OPR) family, denoted as the OPRL/OPR pair. Considering evolutionary perspectives, the OPRL gene cluster in each species likely originates from a replication event of the OPR gene cluster. Gene manipulation and gene expression analysis revealed that CsOPRL influences disease resistance by regulating CsOPR expression in tea plants. Furthermore, the knockout of StOPRL1 in Solanum tuberosum led to aberrant growth characteristics and strong resistance to fungal infection. This study provides insights into a strategy for the screening and functional verification of ECT-lncRNA pairs.

Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP.

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.

Structural insight into the functional regulation of Elongation factor Tu by reactive oxygen species in Synechococcus elongatus PCC 7942.

In cyanobacteria, Elongation factor Tu (EF-Tu) plays a crucial role in the repair of photosystem II (PSII), which is highly susceptible to oxidative stress induced by light exposure and regulated by reactive oxygen species (ROS). However, the specific molecular mechanism governing the functional regulation of EF-Tu by ROS remains unclear. Previous research has shown that a mutated EF-Tu, where C82 is substituted with a Ser residue, can alleviate photoinhibition, highlighting the important role of C82 in EF-Tu photosensitivity. In this study, we elucidated how ROS deactivate EF-Tu by examining the crystal structures of EF-Tu in both wild-type and mutated form (C82S) individually at resolutions of 1.7 Šand 2.0 Šin Synechococcus elongatus PCC 7942 complexed with GDP. Specifically, the GDP-bound form of EF-Tu adopts an open conformation with C82 located internally, making it resistant to oxidation. Coordinated conformational changes in switches I and II create a tunnel that positions C82 for ROS interaction, revealing the vulnerability of the closed conformation of EF-Tu to oxidation. An analysis of these two structures reveals that the precise spatial arrangement of C82 plays a crucial role in modulating EF-Tu's response to ROS, serving as a regulatory element that governs photosynthetic biosynthesis.

Analysis of gut microecological characteristics and differences between children with biliary atresia and non-biliary atresia in infantile cholestasis.

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

A serine carboxypeptidase-like acyltransferase catalyzes consecutive four-step reactions of hydrolyzable tannin biosynthesis in Camellia oleifera.

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.

Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.

ι-Carrageenan catabolism is initiated by key sulfatases in the marine bacterium Pseudoalteromonas haloplanktis LL1.

Marine bacteria contribute substantially to cycle macroalgae polysaccharides in marine environments. Carrageenans are the primary cell wall polysaccharides of red macroalgae. The carrageenan catabolism mechanism and pathways are still largely unclear. Pseudoalteromonas is a representative bacterial genus that can utilize carrageenan. We previously isolated the strain Pseudoalteromonas haloplanktis LL1 that could grow on ι-carrageenan but produce no ι-carrageenase. Here, through a combination of bioinformatic, biochemical, and genetic analyses, we determined that P. haloplanktis LL1 processed a desulfurization-depolymerization sequential pathway for ι-carrageenan utilization, which was initiated by key sulfatases PhSulf1 and PhSulf2. PhSulf2 acted as an endo/exo-G4S (4-O-sulfation-ß-D-galactopyranose) sulfatase, while PhSulf1 was identified as a novel endo-DA2S sulfatase that could function extracellularly. Because of the unique activity of PhSulf1 toward ι-carrageenan rather than oligosaccharides, P. haloplanktis LL1 was considered to have a distinct ι-carrageenan catabolic pathway compared to other known ι-carrageenan-degrading bacteria, which mainly employ multifunctional G4S sulfatases and exo-DA2S (2-O-sulfation-3,6-anhydro-α-D-galactopyranose) sulfatase for sulfate removal. Furthermore, we detected widespread occurrence of PhSulf1-encoding gene homologs in the global ocean, indicating the prevalence of such endo-acting DA2S sulfatases as well as the related ι-carrageenan catabolism pathway. This research provides valuable insights into the enzymatic processes involved in carrageenan catabolism within marine ecological systems.IMPORTANCECarrageenan is a type of linear sulfated polysaccharide that plays a significant role in forming cell walls of marine algae and is found extensively distributed throughout the world's oceans. To the best of our current knowledge, the ι-carrageenan catabolism in marine bacteria either follows the depolymerization-desulfurization sequential process initiated by ι-carrageenase or starts from the desulfurization step catalyzed by exo-acting sulfatases. In this study, we found that the marine bacterium Pseudoalteromonas haloplanktis LL1 processes a distinct pathway for ι-carrageenan catabolism employing a specific endo-acting DA2S-sulfatase PhSulf1 and a multifunctional G4S sulfatase PhSulf2. The unique PhSulf1 homologs appear to be widely present on a global scale, indicating the indispensable contribution of the marine bacteria containing the distinct ι-carrageenan catabolism pathway. Therefore, this study would significantly enrich our understanding of the molecular mechanisms underlying carrageenan utilization, providing valuable insights into the intricate roles of marine bacteria in polysaccharide cycling in marine environments.

Age and BMI have different effects on subcutaneous, visceral, liver, bone marrow, and muscle adiposity, as measured by CT and MRI.

OBJECTIVE: We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots. METHODS: In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements. RESULTS: Of the 168 men, 29% had normal BMI (<24.0 kg/m2), 47% had overweight (24.0-27.9 kg/m2), and 24% had obesity (≥ 28.0 kg/m2). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes. CONCLUSIONS: Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.

PolyQ-expanded ataxin-2 aggregation impairs cellular processing-body homeostasis via sequestering the RNA helicase DDX6.

Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). However, the molecular mechanism underlying how Atx2 aggregation contributes to the proteinopathies remains elusive. Here, we investigated the influence of Atx2 aggregation on the assembly and functionality of cellular processing bodies (P-bodies) by using biochemical and fluorescence imaging approaches. We have revealed that polyQ-expanded (PQE) Atx2 sequesters the DEAD-box RNA helicase (DDX6), an essential component of P-bodies, into aggregates or puncta via some RNA sequences. The N-terminal like-Sm (LSm) domain of Atx2 (residues 82-184) and the C-terminal helicase domain of DDX6 are responsible for the interaction and specific sequestration. Moreover, sequestration of DDX6 may aggravate pre-mRNA mis-splicing, and interfere with the assembly of cellular P-bodies, releasing the endoribonuclease MARF1 that promotes mRNA decay and translational repression. Rescuing the DDX6 protein level can recover the assembly and functionality of P-bodies, preventing targeted mRNA from degradation. This study provides a line of evidence for sequestration of the P-body components and impairment of the P-body homeostasis in dysregulating RNA metabolism, which is implicated in the disease pathologies and a potential therapeutic target.

Synergy of metallic Co and oxygen vacancy sites in Co/Ce-MOF catalysts for efficiently promoting lignin derived phenols and macromolecular lignin hydrodeoxygenation.

The enhanced utilization of biomass-derived chemicals for the generation of high value aromatics through an advanced catalytic strategy has captured considerable attention within the realm of eco-friendly manufacturing. This work presented four innovative three-dimensional rod-shaped mesoporous Ce-based MOF materials, which were coupled with a H-donor solvent to facilitate vanillin hydrodeoxygenation and macromolecular lignin. Under the optimized conditions (30 mg CoCe@C catalyst, 2 MPa N2 pressure, 15 mL isopropanol, 190 °C, and 5 h), the CoCe@C catalyst achieved nearly complete conversion of vanillin and demonstrated 87.8 % selectivity in the hydrogen-donor solvent. The characterization findings suggested that the synergy between metallic Co and oxygen vacancy sites enabled the effective activation of CHO group in vanillin, leading to formation of reactive product MMP. In addition, the optimal CoCe@C catalyst could also achieve macromolecular lignin hydrodeoxygenation to obtain high yield of lignin oil products with narrower molecular weight distribution. This study presented a viable approach for the concurrent utilization of lignin derivatives in the generation of high value fuels and chemicals.

Long- and Intermediate-Term Ambient Particulate Pollution Is Associated with Increased Osteoarthritis Risk: A Population-Based Prospective Analysis.

Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5 (23.32 µg/m3) and PM10 (23.92 µg/m3) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per µg/m3 for annual PM2.5 exposure at below 67.85 µg/m3. Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5 exposure and the three osteoarthritis-related outcomes.

Boosting 5-Hydroxymethylfurfural Electrooxidation by Porous Biochar via Loading Numerous Surface-Exposed Cobalt Phosphonates.

The electrooxidation of 5-hydroxymethylfurfural (HMF) into 2,5-furandicarboxylic acid (FDCA) demonstrated its unique superiority, not only in reducing overpotential and improving energy conversion efficiency for green hydrogen production but also in utilizing abundant biomass resources and producing high-value-added chemicals. However, designing highly efficient electrocatalysts for HMF electrooxidation (HMF-EOR) with low cost and high performance for large-scale production remained a huge challenge. Herein, we introduced an easy one-step activation process to produce P-doped porous biochar loaded with multiple crystal surfaces exposed to CoP2O6 catalysts (CoP2O6@PC), which exhibited outstanding electrooxidation performance. To achieve a current density of 50 mA cm-2, only a low overpotential of 200 mV was needed for the electrooxidation of HMF in 1.0 M KOH + 10 mM HMF. This performance far surpassed that of other similar materials. CoP2O6@PC exhibited outstanding HMF-EOR performance with high conversion (nearly 100%), selectivity (97.1%), faradaic efficiency (95.3%), and robust stability. This work represents a promising strategy to fabricate macroscale and low-cost HMF-EOR electrocatalysts and achieve potential industrial applications of HMF-EOR.

Study on the dynamic response characteristics of lining structures in large-section tunnel blasting using JH-2 model analysis.

The lining structures of tunnels are typically constructed using sprayed or cast concrete materials, and their performance and quality during tunnel excavation and blasting are crucial for the stability and safety of tunnels. Therefore, the safe distance between the lining structure and blasting source should be determined to avoid concrete damage caused by blasting vibrations. In this study, taking the subway tunnel of Danshan Station in Qingdao as an example, the JH-2 model is introduced as the constitutive model of the tunnel blasting simulation, and the JH-2 model parameters of the local surrounding rock are obtained by experiments, and finally the numerical simulation and theoretical verification are carried out to study the safety distance of shotcrete under various safety judgment standards. The results indicate that the JH-2 model can effectively simulate the propagation of stress waves under different media conditions, and the closer the strength parameters and pressure constant of the lining structure are to those of the surrounding rock, the safer the concrete-rock bonding interface. During tunnel blasting construction using the ring blasting method, the peak particle velocity (PPV) of the lining structure increases with an increase in the arch angle. Based on the numerical simulation results, we recommend that concrete lining be constructed at a distance of at least 62 m from the blasting source to avoid damage caused by vibrations. The effect of concrete tensile failure caused by longitudinal stress is much smaller than the damage to the bonding interface caused by the PPV and can be neglected.

Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Relationships between oral function, dietary intake and nutritional status in older adults aged 75 years and above: a cross-sectional study.

BACKGROUND: Malnutrition is related to impaired oral health and function that causes poor dietary intake, declining the general health of older adults. The role of dietary intake in the association between oral function and nutritional status of Chinese older adults (aged 75 and above) was examined in this cross-sectional study. METHODS: Through the randomized cluster sampling method, 267 older adults living in rural areas of Qingdao, Shandong (aged 81.4 ± 4.3, 75-94 years) were chosen as the primary research participants. A Mini Nutritional Assessment - Short Form was used to determine nutritional status, and Food Frequency Questionnaire and 24-hour Food Intake Recall were used to assess dietary intake. The oral function was evaluated by analyzing the teeth, oral problems, bite force, tongue pressure, lip sealing pressure, chewing function questionnaire, whole saliva flow rate, 10-Item Eating Assessment Tool, and water swallow test. RESULTS: Based on the MNA-SF score, it was divided into a well-nourished group and a malnutrition group, with the malnutrition group comprising 40.6% of participants. The participants in the malnutrition group showed a higher rate of xerostomia, lower bite force, tongue pressure, and lip sealing pressure, and higher Chewing Function Questionnaire and 10-Item Eating Assessment Tool scores. Furthermore, their plant fat, iron, cereals and potatoes, vegetables, fruits, and seafood intake were relatively low. The regression model indicated that exercise frequency, stroke, chewing and swallowing function, intake of vegetables and fruits were risk factors for nutritional status of older adults. CONCLUSION: Malnutrition was relatively common among the Chinese older adults aged 75 and above, and it was significantly correlated with exercise frequency, stroke, chewing and swallowing function, and intake of vegetables and fruits. Therefore, nutrition management should be carried out under the understanding and guidance of the oral function and dietary intake of the older adults.

Genotype Distribution and Prevalence of High-Risk Human Papillomavirus among Pregnant Women and Maternal-Fetal Pregnancy Outcomes in a Tertiary Hospital in Beijing, China.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is the primary reason for cervical cancer and precancerous lesions in females. Specific immune alterations in pregnancy led to greater HR-HPV replication and reduced clearance of HR-HPV infection. This study retrospectively obtained and analyzed data from a tertiary hospital in Beijing, China. We aimed to ascertain both the genotype distribution and prevalence of HR-HPV in pregnant females. Moreover, we sought to analyze the association of HR-HPV with maternal-fetal pregnancy outcomes. METHODS: The retrospective observational cohort study was divided into two parts. Part I evaluated the genotype distribution and prevalence of HR-HPV. It encompassed 6285 pregnant women who underwent a routine pregnancy check-up, Thin Prep cytology test (TCT), and HR-HPV diagnosis during weeks 12-14 of gestation between January 1, 2013, and December 31, 2021. Part II analyzed the association between HR-HPV infection and maternal-fetal pregnancy outcome. Through a nearest-neighbor 1:1 propensity score matching (PSM), we matched HR-HPV-positive and HR-HPV-negative pregnant women using caliper width equal to 0.02. After PSM, 171 HR-HPV-positive and 171 HR-HPV-negative pregnant women were included to analyze the association between HR-HPV infection and maternal-fetal pregnancy outcome. RESULTS: In total 737 (11.73%) pregnant women were HR-HPV positive. The five most common genotypes of HR-HPV were HPV-52 (2.90%), HPV-58 (2%), HPV-16 (1.94%), HPV-51 (1.38%), and HPV-39 (1.29%). As for age-specific HPV prevalence, a "U-shaped" pattern was observed. The first and second peaks were detected in pregnant females aged <25 years and those aged ≥35 years, respectively. Our study found no significant difference between the HR-HPV-positive and the HR-HPV-negative pregnant females in the following maternal-fetal pregnancy outcomes: spontaneous abortion (1.2% for HR-HPV positive, 0% for HR-HPV negative, p = 0.478), preterm delivery (4.7% for HR-HPV positive, 5.3% for HR-HPV negative, p = 0.804), premature rupture of membrane (28.8% for HR-HPV positive, 22.8% for HR-HPV negative, p = 0.216), preeclampsia (7.6% for HR-HPV positive, 7.6% for HR-HPV negative, p = 1), oligohydramnios (8.2% for HR-HPV positive, 7% for HR-HPV negative, p = 0.683), fetal growth restriction (1.8% for HR-HPV positive, 0.6% for HPV negative, p = 0.615), placenta previa (1.2% for HR-HPV positive, 0.6% for HR-HPV negative, p = 1), postpartum hemorrhage (8.9% for HR-HPV positive, 11.2% for HR-HPV negative, p = 0.47). There was also no significant difference in delivery mode or birth weight between the two groups. CONCLUSIONS: HPV-16, 52, and 58 were the most prevalent infection genotypes in pregnant females. The study showed no significant differences between HR-HPV-positive and HR-HPV-negative groups in the maternal-fetal pregnancy outcomes.

Combination therapy involving HSP90 inhibitors for combating cancer: an overview of clinical and preclinical progress.

The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.

Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma.

Purpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored. Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR. Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells. Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.