[Clinical efficacy of double-bundle and double-tunnel enhanced reconstruction in the treatment of anterior cruciate ligament injury].

OBJECTIVE: To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL) training injuries. METHODS: Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed. All the cases were underwent ligament reconstruction surgery. Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group, including 13 males and 1 female, aged from 22 to 31 years old with an average of (27.07±7.28) years old, autogenous hamstring tendon was used for ligament reconstruction. There were 15 patients in the enhanced reconstruction group, including 13 males and 2 females, aged from 25 to 34 years old with an average of (29.06±4.23) years old, double tunnel ligament reconstruction, the autogenous hamstring muscle was used as the anteromedial bundle, and the posterolateral bundle was replaced by a high-strength line. The difference between knee tibial anterior distance, Lysholm score, International Knee Literature Committee (IKDC) subjective score, Tegner motor level score and visual analog scale (VAS) at 6th and 12th months after the surgery, limb symmetry index (LSI) were recorded at the last follow-up and surgery-related adverse effects during follow-up. RESULTS: All patients were followed up, ranged from 13 to 15 months with an average of (13.7±0.8) months. There were no serious adverse reactions related to surgery during the period. There was no statistical difference between the preoperative general data and the observation index of the two groups (P>0.05). The difference in tibial anterior distance at 6 and 12 months in the enhanced reconstruction group (1.45±0.62) mm and (1.74±0.78) mm which were lower those that in the conventional reconstruction group (2.42±0.60) mm and (2.51±0.63) mm(P<0.05). There was no significant difference in postoperative Lysholm score, Tegner motor level score, IKDC score, VAS, and limb symmetry index at the last follow-up(P>0.05). CONCLUSION: The enhanced reconstruction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique. The short-term curative effect is satisfactory, and it is suitable for the group with high sports demand.

The Yellow River is the key corridor for Tamarix austromongolica to disperse from Asia inlands to east seashores.

Plants of the Tamarix L. genus (Tamaricaceae) mainly occur in arid inlands of Asia, but a few species occur in the coastal areas of China, and the Yellow River may account for this. This study was conducted to elucidate whether and how the Yellow River affects the pattern and development of the Tamarix genus, involving two critical species of Tamarix austromongolica Nakai and Tamarix chinensis Lour. With geographical distribution data, relationships of T. austromongolica with the Yellow River and the pertaining watershed were examined using the method of random permutation. The base-diameter structures of T. austromongolica populations were investigated and compared between different riparian lands that suffer discriminative water inundation. The nearest distances from T. austromongolica locations to the Yellow River and the pertaining watershed were significantly lower than the theoretical expectations in the condition of random distribution (p < .05). In many riparian lands along the Yellow River, wild T. austromongolica populations occurred with vigorous juveniles, despite frequent human disturbances. In coastal areas near the present estuary of the river, wild T. austromongolica plants were still found. In T. austromongolica populations near the Yellow River and sea, the rates of juvenile plants were significantly higher than in other populations situated farther from the river or sea. These findings suggest that the Yellow River can facilitate the eastward dispersal of Tamarix plants that reasonably caused the evolution from T. austromongolica to T. chinensis in ancient coasts in the China east.

[Effectiveness analysis of double EndoButton suture fixation Latarjet procedure for treatment of anterior shoulder dislocation with glenoid bone defect caused by military training injuries].

Objective: To investigate the effectiveness of double EndoButton suture fixation Latarjet procedure in the treatment of shoulder anterior dislocation with glenoid bone defect caused by military training injuries. Methods: The clinical data of 14 patients with anterior shoulder dislocation with glenoid bone defect due to military training injuries who met the selection criteria and admitted between August 2021 and December 2022 were retrospectively analyzed. All patients were male, the age ranged from 21 to 38 years, with an average of 26.8 years. The time from initial dislocation to operation was 6-15 months, with an average of 10.2 months. Anterior shoulder dislocation occurred 5-12 times, with an average of 8.2 times. All glenoid bone defects were more than 10%, including 5 cases of 10%-15%, 8 cases of 15%-20%, and 1 case of 24%. All patients were treated by double EndoButton suture fixation Latarjet procedure. The operation time and complications were recorded. The shoulder function and pain were evaluated by the American Association for Shoulder and Elbow Surgery (ASES) score, Rowe score, Instability Severity Index Score (ISIS), and visual analogue scale (VAS) score before and after operation. The range of motion of the shoulder was recorded, including forward flexion, 0° external rotation, and abduction 90° external rotation. The position, healing, and resorption of the bone mass were evaluated by three-dimensional CT of shoulder joint after operation. Results: All patients successfully completed the operation, and the operation time was 100-150 minutes, with an average of 119.7 minutes. There was no complications such as infection, vascular and nerve injury. All patients were followed up 12-20 months, with an average of 15.6 months. During the follow-up, 4 patients had bone mass separation, absorption, and recurrent anterior dislocation, and the shoulder joint fear test was positive. Imaging of the remaining patients showed that the bone mass healed well, no anterior dislocation recurrence occurred, and the healing time was 3-7 months (mean, 4.7 months). At last follow-up, the range of motion, ASES score, Rowe score, ISIS score, and VAS score of the patients significantly improved when compared with those before operation ( P<0.05). Conclusion: The effectiveness of double EndoButton suture fixation Latarjet procedure for the treatment of anterior shoulder dislocation with glenoid bone defect caused by military training injury is satisfactory.

[Application of LU-tarjet congruent-arc technique in treatment of recurrent shoulder dislocation with huge glenoid defect].

Objective: To investigate the early effectiveness of the limited unique coracoid osteotomy suture button fixation Latarjet (LU-tarjet)-congruent-arc (CA) technique (LU-tarjet-CA) in treating recurrent shoulder dislocations with huge glenoid defect. Methods: The clinical data of 12 patients with recurrent shoulder dislocation and huge glenoid defect who met the selection criteria and treated with arthroscopic LU-tarjet-CA between January 2021 and December 2023 were retrospectively analyzed. The cohort included 8 males and 4 females, aged 20-40 years with an average age of 30.4 years. The range of glenoid bone loss was 30%-40%, with an average of 35.5%. The time from symptom onset to hospital admission ranged from 1 to 36 months, with an average of 18.5 months. The University of California Los Angeles (UCLA) score, American Association for Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, and Rowe score were used to evaluate shoulder function preoperatively and at 3, 6, and 12 months postoperatively. CT three-dimensional (3D) reconstruction was used to assess coracoid healing and plasticity at 3, 6, and 12 months postoperatively. Subjective satisfaction of patient was recorded at last follow-up. Results: All incisions healed by first intention, with no incision infection or nerve injury. All 12 patients were followed up 12 months. One patient developed Propionibacterium acnes infection within the joint postoperatively and recovered after initial arthroscopic debridement and anti-inflammatory treatment. At 3 months after operation, CT 3D-reconstruction showed 1 case of complete coracoid absorption; neither of these two patients experienced redislocation. The remaining patients exhibited partial coracoid absorption but displayed local reshaping, filling the preoperative defect area, and bony fusion between the coracoid and the glenoid. At last follow-up, 9 patients (75%) were very satisfied with the outcome, and 3 patients (25%) were satisfied; the satisfied patients experienced postoperative shoulder stiffness caused by suboptimal functional exercise but did not have impaired daily life activities. The UCLA score, ASES score, Walch-Duplay score, and Rowe score at 3, 6, and 12 months postoperatively were significantly better than preoperative scores, and each score improved further over time postoperatively, with significant differences between different time points ( P<0.05). Conclusion: The arthroscopic LU-tarjet-CA technique for treating recurrent shoulder dislocations with huge glenoid defect can achieve the surgical objective of bony blockade and filling bone defects to prevent shoulder dislocation, thereby improving patients' quality of life and shoulder joint function and stability.

Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

NR4A1 transcriptionally regulates the differentiation of stem-like CD8+ T cells in the tumor microenvironment.

CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

Multidimensional influencing factors of postpartum depression based on the perspective of the entire reproductive cycle: evidence from western province of China.

OBJECTIVE: China has a serious burden of Postpartum depression (PPD). In order to improve the current situation of high burden of PPD, this study explores the factors affecting PPD from the multidimensional perspectives with physiology, family support and social support covering the full-time chain of pre-pregnancy-pregnancy-postpartum. METHODS: A follow-up survey was conducted in the Qujing First People's Hospital of Yunnan Province from 2020 to 2022, and a total of 4838 pregnant women who underwent antenatal checkups in the hospital were enrolled as study subjects. Mothers were assessed for PPD using the Edinburgh Postnatal Depression Scale (EPDS), and logistic regression was used to analyse the level of mothers' postnatal depression and identify vulnerability characteristics. RESULTS: The prevalence of mothers' PPD was 46.05%, with a higher prevalence among those who had poor pre-pregnancy health, had sleep problems during pregnancy, and only had a single female fetus. In the family support dimension, only family care (OR = 0.52, 95% CI 0.42-0.64) and only other people care(OR = 0.78, 95% CI 0.64-0.96) were the protective factors of PPD. The experience risk of PPD was higher among mothers who did not work or use internet. CONCLUSION: The PPD level in Yunnan Province was significantly higher than the global and Chinese average levels. Factors affecting mothers' PPD exist in all time stages throughout pregnancy, and the influence of family support and social support on PPD shouldn't be ignored. There is an urgent need to extend the time chain of PPD, move its prevention and treatment forward and broaden the dimensions of its intervention.

Potential Function of 3,5-Dihydroxy-4-Methoxybenzyl Alcohol from Pacific Oyster (Crassostrea gigas) in Brain of Old Mice.

SCOPE: 3,5-Dihydroxy-4-methoxybenzyl alcohol (DHMBA) is found in oyster extracts in recent years and is reported to have antioxidant activity. Although it has been reported to be protective in various models of oxidative stress, the therapeutic effect of DHMBA on neurological damage caused by aging remains to be demonstrated. METHODS AND RESULTS: The present study investigates the potential functions of DHMBA in brain of old C57BL/6J mice and aging cell model. Administration of DHMBA improves working memory, reduces anxiety behavior, decreases the expression levels of cell cycle proteins, cycin-dependent kinase inhibitor 1(P21) and peptidase inhibitor 16(P16)  and inhibits neuronal loss in old mice. The data obtained from the aging cell model are consistent with those from the old mice. The interaction between DHMBA and Kelch-like ECH-associated protein 1 (Keap1) is predicted by molecular docking assay, and then it is verified by co-immunopricipitation (CoIP) that factor red lineage 2-related factor 2 (Nrf2)-Keap1 protein-protein interaction is inhibited by DHMBA. Protein levels of Nrf2 and its target genes, such as glutathione peroxidase 4(GPX4) and heme oxygenase 1 (HO-1), are detected in old mice and aging cell model. CONCLUSION: This study provides new evidence that explores the antioxidant mechanism of DHMBA and implies a potential role of DHMBA on antiaging in brain.

An optimized water table depth detected for mitigating global warming potential of greenhouse gas emissions in wetland of Qinghai-Tibetan Plateau.

Climate change and human activities have intensified variations of water table depth (WTD) in wetlands around the world, which may strongly affect greenhouse gas emissions. Here, we analyzed how emissions of CO2, CH4, and N2O from the Zoige wetland on the Qinghai-Tibetan Plateau (QTP) vary with the WTD. Our data indicate that the wetland shows net positive global warming potential (11.72 tCO2-e ha-1 yr-1), and its emissions of greenhouse gases are driven primarily by WTD. Our analysis suggests that an optimal WTD exists, which at our study site was approximately 18 cm, for mitigating increases in global warming potential from the wetland. Our study provides insights into how climate change and human acitivies affect greenhouse gas emissions from alpine wetlands, and they suggest that water table management may be effective at mitigating future increases in emissions.

Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro.

With the inappropriate use of antibiotics, antibiotic resistance has emerged as a major dilemma for patients infected with Pseudomonas aeruginosa. Elastase B (LasB), a crucial extracellular virulence factor secreted by P. aeruginosa, has been identified as a key target for antivirulence therapy. Quercetin, a natural flavonoid, exhibits promising potential as an antivirulence agent. We aim to evaluate the impact of quercetin on P. aeruginosa LasB and elucidate the underlying mechanism. Molecular docking and molecular dynamics simulation revealed a rather favorable intermolecular interaction between quercetin and LasB. At the sub-MICs of ≤256 µg/ml, quercetin was found to effectively inhibit the production and activity of LasB elastase, as well as downregulate the transcription level of the lasB gene in both PAO1 and clinical strains of P. aeruginosa. Through correlation analysis, significant positive correlations were shown between the virulence gene lasB and the QS system regulatory genes lasI, lasR, rhlI, and rhlR in clinical strains of P. aeruginosa. Then, we found the lasB gene expression and LasB activity were significantly deficient in PAO1 ΔlasI and ΔlasIΔrhlI mutants. In addition, quercetin significantly downregulated the expression levels of regulated genes lasI, lasR, rhlI, rhlR, pqsA, and pqsR as well as effectively attenuated the synthesis of signaling molecules 3-oxo-C12-HSL and C4-HSL in the QS system of PAO1. Quercetin was also able to compete with the natural ligands OdDHL, BHL, and PQS for binding to the receptor proteins LasR, RhlR, and PqsR, respectively, resulting in the formation of more stabilized complexes. Taken together, quercetin exhibits enormous potential in combating LasB production and activity by disrupting the QS system of P. aeruginosa in vitro, thereby offering an alternative approach for the antivirulence therapy of P. aeruginosa infections. KEY POINTS: • Quercetin diminished the content and activity of LasB elastase of P. aeruginosa. • Quercetin inhibited the QS system activity of P. aeruginosa. • Quercetin acted on LasB based on the QS system.

[Retrospective analysis and comparison of total internal disability preservation technique and standardized reconstruction technique].

OBJECTIVE: To investigate the efficacy and clinical results of total internal protection technique in anterior cruciate ligament reconstruction. METHODS: A total of 56 patients undergoing anterior cruciate ligament reconstruction treated from January 2018 to December 2019 were selected. According to the different surgical methods, they were divided into total internal reconstruction group and standard bone tunnel group. There were 21 patients in the total internal reconstruction group, including 15 males and 6 females, aged from 20 to 48 with an average of (35.6±6.7) years old, and 35 patients in the standard tibial tunnel group, including 26 males and 9 females, aged 22 to 51 years old with an average of (33.7±9.6) years old. Preoperative examination of Lachman test was positive, magnetic resonance indicated anterior cruciate ligament rupture. There were no significant differences between the two groups in age, sex, body mass index, time from injury to ACL reconstruction, combined meniscus injury and operation method, operation time, ligament diameter, ligament length and other general information. Postoperative evaluation included operation duration, length and diameter of transplanted tendon after braid. International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner score and perioperative complications 2 years after surgery. RESULTS: Both groups were followed up, ranging from 24 to 30 months with an average of (26.9±3.4) months. Postoperative incision healing was good, and no failure or joint infection occurred at the last follow-up. There was no statistically significant difference between the two groups in IKDC score, Lysholm score and Tegner score before, 1 year and 2 years after surgery. However, IKDC score, Lysholm score and Tegner score at 1 year and 2 years after surgery. CONCLUSION: The same postoperative function and stability of knee joint can be obtained by both the residual whole technique and the standardized reconstruction technique. In the residual whole group, only the semitendinosus muscle is taken, and the femoral thin muscle is retained, with greater tibial bone mass preserved, which is safe and effective in clinical practice.

More enhanced non-growing season methane exchanges under warming on the Qinghai-Tibetan Plateau.

Uncertainty in methane (CH4) exchanges across wetlands and grasslands in the Qinghai-Tibetan Plateau (QTP) is projected to increase due to continuous permafrost degradation and asymmetrical seasonal warming. Temperature plays a vital role in regulating CH4 exchange, yet the seasonal patterns of temperature dependencies for CH4 fluxes over the wetlands and grasslands on the QTP remain poorly understood. Here, we demonstrated a stronger warming response of CH4 exchanges during the non-growing season compared to the growing season on the QTP. Analyzing 9745 daily observations and employing four methods -regression fitting of temperature-CH4 flux, temperature dependence calculations, field-based and model-based control experiments-we found that warming intensified CH4 emissions in wetlands and uptakes in grasslands. Specifically, the average reaction intensity in the non-growing season surpasses that in the growing season by 1.89 and 4.80 times, respectively. This stronger warming response of CH4 exchanges during the non-growing season significantly increases the regional CH4 exchange on the QTP. Our research reveals that CH4 exchanges in the QTP have a higher warming sensitivity in non-growing seasons, which meanwhile are dominated by a larger warming rate than the annual average. The combined effects of these two factors will significantly alter the CH4 source/sink on the QTP. Neglecting these impacts would lead to inaccurate estimations of CH4 source/sink over the QTP under climate warming.

NlpI-Prc Proteolytic Complex Mediates Peptidoglycan Synthesis and Degradation via Regulation of Hydrolases and Synthases in Escherichia coli.

Balancing peptidoglycan (PG) synthesis and degradation with precision is essential for bacterial growth, yet our comprehension of this intricate process remains limited. The NlpI-Prc proteolytic complex plays a crucial but poorly understood role in the regulation of multiple enzymes involved in PG metabolism. In this paper, through fluorescent D-amino acid 7-hydroxycoumarincarbonylamino-D-alanine (HADA) labeling and immunolabeling assays, we have demonstrated that the NlpI-Prc complex regulates the activity of PG transpeptidases and subcellular localization of PBP3 under certain growth conditions. PBP7 (a PG hydrolase) and MltD (a lytic transglycosylase) were confirmed to be negatively regulated by the NlpI-Prc complex by an in vivo degradation assay. The endopeptidases, MepS, MepM, and MepH, have consistently been demonstrated as redundantly essential "space makers" for nascent PG insertion. However, we observed that the absence of NlpI-Prc complex can alleviate the lethality of the mepS mepM mepH mutant. A function of PG lytic transglycosylases MltA and MltD as "space makers" was proposed through multiple gene deletions. These findings unveil novel roles for NlpI-Prc in the regulation of both PG synthesis and degradation, shedding light on the previously undiscovered function of lytic transglycosylases as "space makers" in PG expansion.

Effect of piperine on the inhibitory potential of MexAB-OprM efflux pump and imipenem resistance in carbapenem-resistant Pseudomonas aeruginosa.

The escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to global public health through the spread of its 'high-risk' clones. Immediate and decisive research into antimicrobial agents against CRPA is crucial for the development of effective measures and interventions. Overexpression of the MexAB-OprM efflux pump is one of the major mechanisms of CRPA. Since the active efflux of antibacterial agents plays a significant role in mediating drug resistance in CRPA, the inhibition of efflux pumps has become a promising strategy to restore antibacterial potency. Piperine (PIP) has been proven to be a promising efflux pump inhibitor in some bacteria. However, there are no studies on whether PIP can act as a potential efflux pump inhibitor in CRPA. The present study aimed to identify the antibacterial activity of PIP against CRPA and to evaluate the effect on the MexAB-OprM efflux pump. Molecular docking was used to analyze the possible interaction of PIP with the proteins of the MexAB-OprM efflux pump in CRPA. The effect of PIP on the expression of the MexAB-OprM efflux pump was investigated by real-time quantitative PCR (qPCR) and ethidium bromide accumulation efflux assay. The effect of PIP on CRPA imipenem (IPM) resistance was investigated by the checkerboard dilution method. The results demonstrated that PIP exhibited the lowest binding affinity of -9.1 kcal towards efflux pump proteins. A synergistic effect between PIP and IPM on CRPA was observed. More importantly, PIP effectively hindered the efflux of ethidium bromide and IPM by up-regulating MexR gene expression while down-regulating MexA, MexB, and OprM gene expressions. In conclusion, PIP could enhance the antibacterial activity of IPM by inhibiting the MexAB-OprM efflux pump. Our work proved that PIP had the potential to be an efflux pump inhibitor of CRPA.

Biomechanical improvement of anterior talofibular ligament by augmentation repair of ligament advance reinforcement system: a cadaver study.

BACKGROUND: Ankle sprain are one of the most frequent sports injuries. Some individuals will develop chronic lateral ankle instability (CLAI) after ankle sprain and suffer from recurrent ankle sprain. Current surgical treatment of CAI with anterior talofibular ligament (ATFL) rupture fails to restore the stability of the native ATFL. Ligament Advance Reinforcement System (LARS) augmentation repair of ATFL was developed to improve its primary stability after repaired. METHODS: This study was performed to evaluate whether LARS augmentation repair of ATFL had similar stability as the modified Broström repair and the intact ATFL to maintain ankle construct stability. Standardized surgical techniques were performed on eighteen fresh frozen cadaver ankle specimens. The intact ATFL group has just undergone an ATFL exploratory surgery. The modified Broström procedure is based on anatomical repair of the ATFL with a 2.9 mm suture anchor, and the LARS procedure is an augmentation procedure of the ATFL using LARS ligaments based on the modified Broström procedure. A dynamic tensile test machine was used to assess load-to-failure testing in the three groups. The ultimate failure load and stiffness were calculated and reported from the load-displacement curve. A one-way analysis of variance was used to detect significant differences (p < 0.05) between the LARS augmentation repair, the modified Broström repair and the intact ATFL, followed by least significant difference (LSD) post-hoc tests. RESULTS: The LARS augmentation repair group showed an increased in ultimate failure to load and stiffness compared to the other two groups. There were no significant differences in ultimate failure to load and stiffness between the modified Broström and the intact ATFL, the LARS ligament for ATFL augmentation allows for improved primary stability after repair and reduced stress on the repaired ATFL, which facilitates healing of the remnant ligament. CONCLUSIONS: The LARS augmentation repair of ATFL represents a stable technique that may allow for the ankle stability to be restored in patients with CAI after surgery.

A varying-parameter fixed-time gradient-based dynamic network for convex optimization.

We focus on the fixed-time convergence and robustness of gradient-based dynamic networks for solving convex optimization. Most of the existing gradient-based dynamic networks with fixed-time convergence have limited ability to resist interferences of noises. To improve the convergence of the gradient-based dynamic networks, we design a new activation function and propose a gradient-based dynamic network with fixed-time convergence. The proposed dynamic network has a smaller upper bound of the convergence time than the existing dynamic networks with fixed-time convergence. A time-varying scaling parameter is employed to speed up the convergence. Our gradient-based dynamic network is proved to be robust against bounded noises and is able to resist the interference of unbounded noises. The numerical tests illustrate the effectiveness and superiority of the proposed network.

Microstructurally and mechanically tunable acellular hydrogel scaffold using carboxymethyl cellulose for potential osteochondral tissue engineering.

In tissue engineering, scaffold microstructures and mechanical cues play a significant role in regulating stem cell differentiation, proliferation, and infiltration, offering a promising strategy for osteochondral tissue repair. In this present study, we aimed to develop a facile method to fabricate an acellular hydrogel scaffold (AHS) with tunable mechanical stiffness and microstructures using carboxymethyl cellulose (CMC). The impacts of the degree of crosslinking, crosslinker length, and matrix density on the AHS were investigated using different characterization methods, and the in vitro biocompatible of AHS was also examined. Our CMC-based AHS showed tunable mechanical stiffness ranging from 50 kPa to 300 kPa and adjustable microporous size between 50 µm and 200 µm. In addition, the AHS was also proven biocompatible and did not negatively affect rabbit bone marrow stem cells' dual-linage differentiation into osteoblasts and chondrocytes. In conclusion, our approach may present a promising method in osteochondral tissue engineering.

Characterization and genomic analysis of a broad-spectrum lytic phage HZ2201 and its antibiofilm efficacy against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a clinically common conditionally pathogenic bacterium, and the abuse of antibiotics has exacerbated its drug resistance in recent years. This has resulted in extensive reports about the usage of Pseudomonas aeruginosa phage as a novel antibacterial drug. In this study, we isolated a novel phage HZ2201 with a broad lytic spectrum. The lytic rate of this phage against Pseudomonas aeruginosa reached 78.38% (29/37), including 25 multi-drug- and carbapenem-resistant Pseudomonas aeruginosa strains. Transmission electron microscopy revealed that phage HZ2201 belongs to the class Caudoviricetes. Biological characterization showed that phage HZ2201 had an latent period of 40 min, a lytic period of 20 min, and a burst size of 440 PFU/cell, with improved tolerance to temperature and pH. Considering genomic analysis, the HZ2201 genome was a circular double-stranded DNA with a size of 45,431 bp and a guanine-cytosine (G + C) content of 52.16%, and contained 3 tRNAs. 27 of the 74 open reading frames (ORFs) annotated by the Rapid Annotation using Subsystem Technology (RAST) tool could be matched to the genomes of known functions, and no genes related to virulence and antibiotic resistance were found. The phylogenetic tree suggests that phage HZ2201 is highly related to the phage ZCPS1 and PaP3, and ORF57 and ORF17 are predicted to encode a holin and an endolysin, respectively. Cell lysis by HZ2201 proceeds through the holin-endolysin system, suggesting that it is a novel phage. Additionally, we demonstrated that phage HZ2201 has a high inhibitory capacity against Pseudomonas aeruginosa biofilms. The results of our study suggest that phage HZ2201 is a novel potential antimicrobial agent for treating drug-resistant Pseudomonas aeruginosa infection.

Temporal trends of breast cancer burden in the Western Pacific Region from 1990 to 2044: Implications from the Global Burden of Disease Study 2019.

INTRODUCTION: Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden. OBJECTIVES: To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement. METHODS: Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years. RESULTS: In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development. CONCLUSIONS: The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.

Berberine ameliorates iron levels and ferroptosis in the brain of 3 × Tg-AD mice.

BACKGROUND: Berberine (BBR) is a natural alkaloid extracted from the herb Coptis chinensis. This compound has the ability to penetrate the blood-brain barrier (BBB) and exhibit neuroprotective value in the treatment of Alzheimer's disease (AD). AD is a neurodegenerative disease characterized by ß-amyloid (Aß) deposition, hyperphosphorylated tau and other characters. Iron accumulation and ferroptosis were also detected in AD brain, which can result in neuronal damage. However, it is still unclear whether BBR can suppress ferroptosis in AD and alleviate its underlying pathology. PURPOSE: This study investigated whether BBR may affect ferroptosis and related signaling pathways in triple transgenic AD (3 × Tg-AD) mice. METHODS: Four-month-old 3 × Tg-AD mice received oral administration of BBR at a dose of 50 mg/kg for 7.5 months. Cognitive function and anxiety levels in mice were assessed using the morris water maze test, open field test, and novel object recognition test. Western blot, immunohistochemistry, and ICP-MS were employed to assess the pathology of AD, brain iron metabolism, and ferroptosis signaling pathways. Transmission electron microscopy was used to detect mitochondrial changes. The synergistic effects of BBR combined with Nrf2 were investigated using molecular docking programs and surface plasmon resonance technology. Co-inmunoprecipitation assay was used to examine the effect of BBR on the binding ability of Nrf2 and Keap1. RESULTS: The results indicated that chronic treatment of BBR mitigated cognitive disorders in 3 × Tg-AD model mice. Reductions in Aß plaque, hyperphosphorylated tau protein, neuronal loss, and ferroptosis in the brains of 3 × Tg-AD mice suggested that BBR could alleviate brain injury. In addition, BBR treatment attenuated ferroptosis, as evidenced by decreased levels of iron, MDA, and ROS, while enhancing SOD, GSH, GPX4, and SLC7A11. Consistent with the in vivo assay, BBR inhibited RSL3-induced ferroptosis in N2a-sw cells. BBR increased the expression levels of GPX4, FPN1 and SLC7A11 by regulating Nrf2 transcription levels, thereby inhibiting ferroptosis. Molecular docking programs and surface plasmon resonance technology demonstrated the direct combination of BBR with Nrf2. Co-inmunoprecipitation analysis showed that BBR inhibited the interaction between Keap1 and Nrf2. CONCLUSION: For the first time, these results showed that BBR could inhibit iron levels and ferroptosis in the brains of 3 × Tg-AD model mice and partially protect against RSL3-induced ferroptosis via the activation of Nrf2 signaling.