Classification of distinct tendinopathy subtypes for precision therapeutics.

Rotator cuff tendinopathy is the most common tendinopathy type with the worst prognosis. Conventional treatments often elicit heterogeneous drug responses due to the diversity of tendinopathy. Hence, this study attempted a classification of 126 diseased tendons into three distinct subtypes with opposite pathogenic mechanisms based on transcriptomic and clinical features. The hypoxic atrophic subtype with white appearance (Hw) exhibits downregulated neovascularization pathways. The inflammatory proliferative subtype with white appearance (Iw) shows a moderate upregulation of inflammatory characteristics. The inflammatory proliferative subtype with red appearance (Ir) exhibits the highest levels of upregulated neovascularization and inflammatory pathways, along with severe joint dysfunction. We then established research models, including subtype-specific simulations in animal models and clinical data analysis. These revealed that glucocorticoid, a controversial commonly used drug, was only effective in treating the Ir subtype. Hence, the tendinopathy subtypes elucidated in this study have significant implications for developing precision treatment of tendinopathy.

Synergistic bioremediation of petroleum-contaminated soil using immobilized consortium of Rhodococcus rhodochrous and Bacillus subtilis laccase.

Petroleum-contaminated soil represents a significant environmental and public health challenge on a global scale. Microbial bioremediation has shown potential, yet the role of enzymes in enhancing petroleum degradation remains underexplored. In this study, the synergistic effects of Rhodococcus rhodochrous (R.rh) and Bacillus subtilis-derived laccase (BsLac) was investigated in the remediation of petroleum-contaminated soil. Immobilized R.rh (PSIMRH) and BsLac (ADIMLac) exhibited higher petroleum degradation rates than their free state, achieving 78.3% and 56.3% degradation in liquid systems, respectively. The combined treatment of PSIMRH and ADIMLac demonstrated a synergistic effect on petroleum degradation, achieving 43.6% with a maximum degradation constant of 0.0335 d-1, representing a 202.7% improvement over untreated soil. PSIMRH enhanced petroleum degradation through microbial metabolism, while ADIMLac accelerated the initial breakdown of complex hydrocarbons into simpler, more bioavailable ones via enzymatic oxidation, providing growth substrates for microbes and significantly improving petroleum degradation rates. The microbial analysis revealed an increase abundance of known petroleum-degrading bacterial genera, including Rhodococcus, Lysobacter, Micromonospora, and Streptomyces. However, the presence of BsLac appeared to reduce the competitive advantage of Rhodococcus, promoting the proliferation of indigenous strains like Lysobacter and Streptomyces. These results suggest that enzyme-microbe synergy can enhance the bioremediation process by altering microbial community dynamics and accelerating petroleum degradation. This study attempts to remediate petroleum-contaminated pollution with the combined use of strains and enzymes, providing a new approach for the remediation of other pollution problems.

The association between oral frailty and HbA1c among older adults with T2DM: the chain mediating effect of nutritional status and physical frailty.

OBJECTIVES: The present study aimed to explore the association between oral frailty and glycated hemoglobin (HbA1c), and the chain mediating role of nutritional status and physical frailty among older adults with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM aged > 60 years were recruited from the endocrinology department of a national metabolic center from October 2023 to March 2024. Oral frailty, nutritional status, and physical frailty were assessed with Oral Frailty Index-8 (OFI-8), the Nutrition Risk Screening 2002 (NRS2002), Fatigue, Resistance, Ambulation, Illness and Loss of Weight Index (FRAIL), respectively. Their HbA1c were collected at the same time. In order to reveal the interaction and influence between multiple variables, chain mediation analyses were conducted using the "Process" macro in SPSS 26.0 to estimate the direct and indirect effects of oral frailty on nutritional status, physical frailty and HbA1c. RESULTS: A total of 292 participants (50.7% male) were enrolled in this study at a median age of 70.0 (65.2, 76.0) years and a T2DM disease duration of (16.5 ± 9.4) years. After adjustment for age, oral frailty of older people with T2DM significantly positively predicted their HbA1c (ß = 0.198, P < 0.001). In addition, oral frailty affect HbA1c through two indirect pathways, including an independent mediating effect of physical frailty (effect = 0.046) and a chain-mediating effect of nutritional status and physical frailty (effect = 0.004). CONCLUSIONS: Our findings suggest that less oral frailty of older adults with T2DM could optimize their nutritional status and physical frailty and, thus, their HbA1c. Consequently, improving oral health is expected to be a promising intervention target for reaching optimal glycaemic control in older adults with T2DM.

Sudden Blindness as the Only Symptom Caused by a Small Sphenoid Sinus Mucocele in a Young Child.

Background: Sphenoid sinus mucocele (SSM) represents a relatively rare disease among pediatric population as compared to adults, with a 1% to 3% incidence of all paranasal sinus mucoceles. Since the initial symptoms varied often, SSM caused blindness was scarcely seen. Case Presentation: Here we described an unusual case of small, isolated SSM causing acute visual loss in a 9-year-old girl. The patient first consulted an ophthalmologist for her right blindness. A diagnosis of SSM was suspected indicated by an orbital MRI scan. Thereafter the patient was referred to our department and an endoscopic sphenoidotomy and optic nerve decompression was performed. Surprisingly, her vision was relieved immediately after surgery, followed by dramatic improvement during the postoperative 20-month follow-up period. Conclusion: To our knowledge, a better understanding of SSM in pediatrics is essential for clinicians, including neurologists, ophthalmologists, and otolaryngologists to make early diagnoses and correct treatment by MRI and CT scan. Prompt surgical intervention of endoscopic transnasal sphenoidectomy is a quite safe, effective, and minimally invasive method for patients.

Impact of caring leadership on nurses' work engagement: examining the chain mediating effect of calling and affective organization commitment.

BACKGROUND: Previous studies have established a positive link between nurse managers' caring leadership and nurses' work engagement, but the processes and conditions through which this leadership style influences positive work behaviors remain largely unexplored. To address this gap and contribute to the existing body of knowledge, we developed a chain-mediated effects model to elucidate the impact of caring leadership on nurses' work engagement and the underlying mechanisms. In this model, we identified professional mission and affective organizational commitment as the mediating variables, offering a novel perspective on the relationship between caring leadership and work engagement. METHODS: A robust multi-center and large-sample cross-sectional survey was conducted, involving 2502 first-line nurses from six general tertiary hospitals across the eastern, central, and western regions of China. The data collection instruments included a comprehensive questionnaire covering demographic information, the caring leadership scale, the Chinese calling scale, the affective organizational commitment scale, and the Utrecht work engagement scale. Data were meticulously screened and analyzed, employing descriptive analysis to summarize the demographic information, correlation analysis to test the relationship among the variables, stepwise regression analysis to explore the mediating role of calling and affective organization commitment, and the bootstrap method to test the chain mediating effect. This rigorous methodology not only ensures the reliability and validity of research findings but also instills confidence in the robustness of this research. RESULTS: The results indicated a positive relationship among caring leadership, calling, affective organizational commitment, and nurses' work engagement (p < 0.001). Specifically, caring leadership was significantly associated with nurses' calling (ß = 0.55, p < 0.001), affective organizational commitment (ß = 0.21, p < 0.001), and work engagement (ß = 0.05, p < 0.001). And the analysis further revealed that calling and affective organizational commitment mediate the process between caring leadership and work engagement(Effect: 0.17, 0.03, 0.05), with a relative effect size of 89.3% for the total indirect effect. These findings highlight the crucial role of these factors in enhancing nurses' work engagement, providing valuable insights for healthcare leaders and policymakers. CONCLUSION: Caring leadership positively predicts nurses' work engagement and indirectly mediates calling and affective organizational commitment. The results of this study revealed that the mechanisms of caring leadership influence nurses' work engagement, which provides a new approach to strengthening nurses' work engagement and improving patient healthcare outcomes and organizational performance. Healthcare organizations face continuous challenges; this study embodies the significance of caring leadership in improving nurses' work experience and increasing their work engagement. Nursing managers should enhance their knowledge of caring leadership and receive caring leadership training, thus actively improving their leadership behaviors in nurse management, enhancing leadership effectiveness, and creating more possibilities for developing healthcare organizations.

Tissue-engineered Bicipital Autologous Tendon Patch Enhances Massive Rotator Cuff Defect Repair in a Rabbit Infraspinatus Tendon Defect Model.

BACKGROUND: Massive rotator cuff defects represent an important source of shoulder pain and functional debilitation, substantially diminishing patients' quality of life. The primary treatment of massive rotator cuff defects includes complete or partial repair and patch augmentation. However, because of the tendon's limited regenerative ability, the tendon retear risk after rotator cuff defect repair is still high. Thus, a new therapy is needed to promote tendon regeneration for repair of massive rotator cuff defects. QUESTIONS/PURPOSES: Using an in vitro analysis, we first asked: (1) What is the biocompatibility and collagen synthesis ability of fibrin glue, and what is the cell growth of tissue-engineered bicipital tendon patches, which is comprised of fibrin glue and biceps tendon tissue particles? Then, using an in vivo animal model of full-thickness defects in the infraspinatus tendon in New Zealand White rabbits, we asked: (2) What is the potential of the tissue-engineered bicipital autologous tendon patch to promote tendon regeneration? METHODS: In vitro experiments were conducted to assess the survival, proliferation, and collagen synthesis ability of tendon stem/progenitor cells cultured in fibrin glue. This was achieved through an assay of live/dead cell viability, cell counting kit-8 (CCK-8) assay, and Sirius red staining, respectively. The in vivo animal study was conducted using 8- to 12-week-old New Zealand White rabbits. The left shoulder of each animal was operated on, with equal numbers of males and females. There were 12 rabbits in the control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch groups at 2-month time point. Through an infraspinatus tendon defect model, the effectiveness of tissue-engineered bicipital autologous tendon patches (patch group) in tendon repair was assessed compared with untreated (control group) and fibrin glue (gel group) treatments in vivo. This assessment included histological evaluation of repaired tissue morphology, transmission electron microscopy (TEM) evaluation of regenerated collagen fibrils, and RNA sequencing to explore the potential mechanisms of tissue-engineered bicipital autologous tendon patches in tendon regeneration. RESULTS: In vitro experiments demonstrated that fibrin glue enhanced the collagen synthesis ability of tendon stem/progenitor cells (0.38 ± 0.02) compared with standard cell culture alone (0.27 ± 0.02, mean difference 0.11 [95% CI 0.07 to 0.14]; p < 0.001). With prolonged cultivation, the cell growth area of tissue-engineered bicipital tendon patches showed a notable increase after culturing for 14 days (78.13% ± 3.68%) compared with 11 days (13.05% ± 8.78%, mean difference -65.08% [95% CI -77.99% to -52.15%]; p＜0.001), 7 days (2.67% ± 2.62%, mean difference -75.46% [95% CI -88.37% to -62.53%]; p＜0.001), and 1 day (0.33% ± 0.30%, mean difference -77.80% [95% CI -90.71% to -64.87%]; p＜0.001). At 3 months after transplantation, in vivo experiments revealed that compared with the control and gel groups, the patch group displayed improved repair outcomes. This was evidenced by better histological scores in the patch group (3.83 ± 2.01) compared with the gel group (10.67 ± 0.58, mean difference 6.84 [95% CI 3.67 to 10.00]; p = 0.001) and control group (10.75 ± 0.66, mean difference 6.92 [95% CI 3.75 to 10.08]; p = 0.001), and by regular alignment and larger diameters of newly formed collagen fibrils in the patch group (77.52 ± 44.41 nm) compared with the control group (53.34 ± 6.64 nm, mean difference 24.18 [95% CI 22.24 to 26.11]; p < 0.001). RNA sequencing analysis revealed that a tissue-engineered bicipital autologous tendon patch facilitated tendon regeneration by modulating the immune response, promoting collagen fibril organization, and alleviating vasoconstriction. CONCLUSION: This animal study demonstrates that the tissue-engineered bicipital autologous tendon patch effectively modulates an immune response and collagen fibril organization, leading to the promotion of tendon regeneration. CLINICAL RELEVANCE: The tissue-engineered bicipital autologous tendon patch represents a promising strategy for tendon regeneration, offering potential in the repair of massive rotator cuff defects during clinical rotator cuff surgery. Subsequent research could focus on large animal experiments using a tissue-engineered bicipital autologous tendon patch to explore their feasibility for clinical translation.

Construction of platelet count-optical method reflex test rules using Micro-RBC#, Macro-RBC%, "PLT clumps?" flag, and "PLT abnormal histogram" flag on the Mindray BC-6800plus hematology analyzer in clinical practice.

OBJECTIVES: Utilizing RBC or PLT-related parameters to establish rules for the PLT-O reflex test can assist laboratories in quickly identifying specimens with interfered PLT-I that require PLT-O retesting. METHODS: Prospective PLT-I and PLT-O testing was performed on 6857 EDTA-anticoagulated whole blood samples, split randomly into training and validation cohorts at a 2:3 ratio. Reflex and non-reflex groups were distinguished based on the differences between PLT-I and PLT-O results. By comparing RBC and PLT parameter differences and flags in the training set, we pinpointed factors linked to PLT-O reflex testing. Utilizing Lasso regression, then refining through univariate and multivariate logistic regression, candidate parameters were selected. A predictive nomogram was constructed from these parameters and subsequently validated using the validation set. ROC curves were also plotted. RESULTS: Significant differences were observed between the reflex and non-reflex groups for 19 parameters including RBC, MCV, MCH, MCHC, RDW-CV, RDW-SD, Micro-RBC#, Micro-RBC%, Macro-RBC#, Macro-RBC%, MPV, PCT, P-LCC, P-LCR, PLR,"PLT clumps?" flag, "PLT abnormal histogram" flag, "IDA Anemia?" flag, and "RBC abnormal histogram" flag. After further analysis, Micro-RBC#, Macro-RBC%,"PLT clumps?", and "PLT abnormal histogram" flag were identified as candidate parameters to develop a nomogram with an AUC of 0.636 (95 %CI: 0.622-0.650), sensitivity of 42.9 % (95 %CI: 37.8-48.1 %), and specificity of 90.5 % (95 %C1: 89.6-91.3 %). CONCLUSIONS: The established rules may help laboratories improve efficiency and increase accuracy in determining platelet counts as a supplement to ICSH41 guidelines.

Unraveling the role of ubiquitin-conjugating enzyme 5 (UBC5) in disease pathogenesis: A comprehensive review.

While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands.

Wettability Behaviour of Metal Surfaces after Sequential Nanosecond and Picosecond Laser Texturing.

This study examines the wettability behaviour of 304 stainless steel (304SS) and Ti-6Al-4V (Ti64) surfaces after sequential nanosecond (ns) and picosecond (ps) laser texturing; in particular, how the multi-scale surface structures created influence the lifecycle of surface hydrophobicity. The effect of different post-process treatments is also examined. Surfaces were analysed using Scanning Electron Microscopy (SEM), a white light interferometer optical profiler, and Energy Dispersive X-ray (EDX) spectroscopy. Wettability was assessed through sessile drop contact angle (CA) measurements, conducted at regular intervals over periods of up to 12 months, while EDX scans monitored elemental chemical changes. The results show that sequential (ns + ps) laser processing produced multi-scale surface texture with laser-induced periodic surface structures (LIPSS). Compared to the ns laser case, the (ns + ps) laser processed surfaces transitioned more rapidly to a hydrophobic state and maintained this property for much longer, especially when the single post-process treatment was ultrasonic cleaning. Some interesting features in CA development over these extended timescales are revealed. For 304SS, hydrophobicity was reached in 1-2 days, with the CA then remaining in the range of 120 to 140° for up to 180 days; whereas the ns laser-processed surfaces took longer to reach hydrophobicity and only maintained the condition for up to 30 days. Similar results were found for the case of Ti64. The findings show that such multi-scale structured metal surfaces can offer relatively stable hydrophobic properties, the lifetime of which can be extended significantly through the appropriate selection of laser process parameters and post-process treatment. The addition of LIPSS appears to help extend the longevity of the hydrophobic property. In seeking to identify other factors influencing wettability, from our EDX results, we observed a significant and steady rate of increase in the carbon content at the surface over the study period.

Defect Engineering in a Nanoporous Thulium-Organic Framework in Catalyzing Knoevenagel Condensation and Chemical CO2 Fixation.

Defect engineering is an extremely effective strategy for modifying metal-organic frameworks (MOFs), which can break through the application limitations of traditional MOFs and enhance their functionality. Herein, we report a highly robust nanoporous thulium(III)-organic framework, {[Tm2(BDCP)(H2O)5](NO3)·3DMF·2H2O}n (NUC-105), with [Tm(COO)2(H2O)]n chains and [Tm2(COO)4(H2O)8] dinuclears as metal nodes and 2,6-bis(2,4-dicarboxylphenyl)-4-(4-carboxylphenyl)pyridine (BDCP) linkers. In NUC-105, each of the four chains of [Tm(COO)2]n and the two rows of [Tm2(COO)4(H2O)8] units is unified by the organic skeleton, resulting in a rectangular nanochannel with dimensions of 15.35 Å × 11.29 Å, which leads to a void volume of 50%. It is worth mentioning that the [Tm2(COO)4(H2O)8] cluster is very rare in terms of its higher level of associated water molecules, implying that the activated host framework can serve as a strong Lewis acid. NUC-105a exhibited great heterogeneous catalytic performance for CO2 cycloaddition with epoxides under the reaction conditions (0.60 mol % NUC-105a, 5.0 mol % n-Bu4NBr, 65 °C, 5 h), ensuring exclusive selectivity and high conversion rates. In addition, NUC-105a's strong catalytic impact on the Knoevenagel condensation of aldehydes and malononitrile can be attributed to the collaboration between the drastically unsaturated Lewis acidic Tm3+ centers and Lewis basic pyridine groups.

Defect-engineered indium-organic framework displays the higher CO2 adsorption and more excellent catalytic performance on the cycloaddition of CO2 with epoxides under mild conditions.

In order to achieve the high adsorption and catalytic performance of CO2, the direct self-assembly of robust defect-engineered MOFs is a scarcely reported and challenging proposition. Herein, a highly robust nanoporous indium(III)-organic framework of {[In2(CPPDA)(H2O)3](NO3)·2DMF·3H2O}n (NUC-107) consisting of two kinds of inorganic units of chain-shaped [In(COO)2(H2O)]n and watery binuclear [In2(COO)4(H2O)8] was generated by regulating the growth environment. It is worth mentioning that [In2(COO)4(H2O)8] is very rare in terms of its richer associated water molecules, implying that defect-enriched metal ions in the activated host framework can serve as strong Lewis acid. Compared to reported skeleton of [In4(CPPDA)2(µ3-OH)2(DMF)(H2O)2]n (NUC-66) with tetranuclear clusters of [In4(µ3-OH)2(COO)10(DMF)(H2O)2] as nodes, the void volume of NUC-107 (50.7%) is slightly lower than the one of NUC-66 (52.8%). However, each In3+ ion in NUC-107 has an average of 1.5 coordinated small molecules (H2O), which far exceeds the average of 0.75 in NUC-66 (H2O and DMF). After thermal activation, NUC-107a characterizes the merits of unsaturated In3+ sites, free pyridine moieties, solvent-free nanochannels (10.2 × 15.7 Å2). Adsorption tests prove that the host framework of NUC-107a has a higher CO2 adsorption (113.2 cm3/g at 273 K and 64.8 cm3/g at 298 K) than NUC-66 (91.2 cm3/g at 273 K and 53.0 cm3/g at 298 K). Catalytic experiments confirmed that activated NUC-107a with the aid of n-Bu4NBr was capable of efficiently catalyzing the cycloaddition of CO2 with epoxides into corresponding cyclic carbonates under the mild conditions. Under the similar conditions of 0.10 mol% MOFs, 0.5 mol% n-Bu4NBr, 0.5 MP CO2, 60 °C and 3 h, compared with NUC-66a, the conversion of SO to SC catalyzed by NUC-107a increased by 21%. Hence, this work offers a valuable perspective that the in situ creation of robust defect-engineered MOFs can be realized by regulating the growth environment.

Fe oxides simultaneously improve stability of Cd and carbon in paddy soil：The underlying influence at aggregate level.

Iron (Fe) oxides have a strong adsorption affinity for Cd and organic carbon (SOC). However, under alternate wet-dry (IF) condition,the influences of Fe oxides on the speciation and disrtribution of Cd and SOC in soil aggregates are unkown. In the present study, soils untreated (S), removed (S-Fe) or added (S+Fe) Fe oxide soils were blended with cadmium chloride solution and cultivated for 56 days under different moisture management practices. Compared with the S-Fe soil, the IF treatment increased the contents of Fe oxide-bound SOC (Fe-OC) and Fe/Mn oxide-bound Cd (Fe/Mn-Cd) by 18.5-29.8-fold and 1.45-2.45-fold, repectively, in the S and S+Fe soils, corresponding to a 36 %-42 % increase in the recalcitrant C pool (RCP) and a 53 %-87 % decrease in the exchangeable Cd content. These results could be attributed to soil particle aggregation and Fe redistribution. Fe addition promoted the transfer of Cd/SOC accumulated in microaggregates to macroaggregates and increased the variable negative charge content in macroaggregates and the adsorption capacity of macroaggregates for Cd/SOC. More Cd/SOC accumulated in macroaggregates in Fe oxide-bound form, which reduced the risk of Cd migration and Cd availability and increased the physical protection of SOC. Therefore, Fe oxide has great potential to simultaneously reduce carbon emissions and cadmium toxicity in paddy soil.

Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells.

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their treatment remains a major challenge. Here, we report a nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1S, 3R)-RSL3 (RSL3) are integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits through biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs and released in a synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis to stimulate adaptive immunity and enhance interferon gamma (IFNγ) secretion by CD8+ T cells to downregulate SLC7A11 and SLC3A2 for blocking glutathione biosynthesis. Meanwhile, Ni-dependent STAT3 inhibition also upregulates ACSL4 through downstream signaling and IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation to induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 also impairs the immunosuppressive M2-like tumor-associated macrophages, while Ca2+ ions released from degraded ACP could chelate with lipid peroxides in ferroptotic CSCs to avoid CD8+ T-cell inhibition, thus boosting the effector function of activated CD8+ T cells. This study offers a cooperative ferroptosis-immunotherapeutic approach for the treatment of refractory cancer.

Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

Study on the interaction mechanism of whey protein isolate with phosphatidylcholine: By multispectral methods and molecular docking.

The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α-lactalbumin, ß-lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at -5.59, -6.71, and -7.85 kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC-WPI interaction mechanism in food.

Effects of non-pharmacological interventions for adults with subjective cognitive decline: a network meta-analysis and component network meta-analysis.

BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.

Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China.

AIMS: Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations. METHODS: This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses. RESULTS: Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and BRAF gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates. CONCLUSION: p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study's findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.

Adherence to therapeutic gastroscopy guidelines for acute esophageal food bolus impaction: Impact on adverse outcomes and length of stay.

Background and Aim: According to the European Society of Gastrointestinal Endoscopy (ESGE), gastroscopy should be conducted within 6 h for complete obstruction and 24 h for incomplete obstruction due to food bolus impaction. This study explores whether adults with acute esophageal food bolus (FB) impaction experience adverse outcomes when their time to esophagogastroduodenoscopy (EGD) deviates from the recommended guidelines. Methods: A retrospective review was performed on the records of 248 patients who presented at the study site between 2015 and 2022 with symptoms of FB impaction. Results: Two hundred and forty-eight patients underwent EGD for FB impaction. Grade 1 (erosion, ulceration), Grade 2 (tear), and Grade 3 (perforation) complications were present in 31.6%, 6.9%, and 0.8% of cases, respectively. Of the 134 (54.0%) patients with complete obstruction, 51 (38.1%) received EGD within the recommended 6 h. Of the 114 (46%) patients with incomplete obstructions, 93 (81.6%) received EGD within the recommended 24 h. There was no statistically significant correlation between length of stay (LOS) post-EGD and any of ingestion to presentation time, presentation to EGD time, or ingestion to EGD time. Age and complication level were greater predictors of longer LOS than presentation to EGD time. Patients who presented in hours were significantly more likely to receive EGD within the 6- and 24-h guidelines than those who presented out of hours (50.7% vs 22.0%). Conclusion: Neither time to EGD from ingestion of food bolus nor time to EGD from hospital presentation correlated with complication rate, complication severity, or length of stay post-EGD.

Novel methods to diagnose rotator cuff tear and predict post-operative Re-tear: Radiomics models.

Objective: To validated a classifier to distinguish the status of rotator cuff tear and predict post-operative re-tear by utilizing magnetic resonance imaging (MRI) markers. Methods: This retrospective study included patients with healthy rotator cuff and patients diagnosed as rotator cuff tear (RCT) by MRI. Radiomics features were identified from the pre-operative shoulder MRI and selected by using maximum relevance minimum redundancy (MRMR) methods. A radiomics model for diagnosis of RCT was constructed, based on the 3D volume of interest (VOI) of supraspinatus. Another model for the prediction of rotator re-tear after rotator cuff repair (Re-RCT) was constructed based on VOI of humerus, supraspinatus, infraspinatus and other clinical parameters. Results: The model for diagnosing the status of RCT produced an area under the receiver operating characteristic curve (AUC) of 0.989 in the training cohort and 0.979 for the validation cohort. The radiomics model for predicting Re-RCT produced an AUC of 0.923 ± 0.017 for the training dataset and 0.790 ± 0.082 for the validation dataset. The nomogram combining radiomics features and clinical factors yielded an AUC of 0.961 ± 0.020 for the training dataset and 0.808 ± 0.081 for the validation dataset, which displayed the best performance among all models. Conclusion: Radiomics models for the diagnosis of rotator cuff tear and prediction of post-operative Re-RCT yielded a decent prediction accuracy.

Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway.

Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit­8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylin­eosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcription­quantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786­O and ACHN) than the effect on normal renal tubular epithelial cell (HK­2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dose­dependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.