Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.

BACKGROUND: Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties. RESULTS: By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level. CONCLUSION: This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.

Top 100 cited research on COVID-19 vaccines: A bibliometric analysis and evidence mapping.

The outbreak of the COVID-19 has seriously affected the whole society, and vaccines were the most effective means to contain the epidemic. This paper aims to determine the top 100 articles cited most frequently in COVID-19 vaccines and to analyze the research status and hot spots in this field through bibliometrics, to provide a reference for future research. We conducted a comprehensive search of the Web of Science Core Collection database on November 29, 2023, and identified the top 100 articles by ranking them from highest to lowest citation frequency. In addition, we analyzed the year of publication, citation, author, country, institution, journal, and keywords with Microsoft Excel 2019 and VOSviewer 1.6.18. Research focused on vaccine immunogenicity and safety, vaccine hesitancy, and vaccination intention.

IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation.

IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Gas displacement characteristics during the water wetting process of gas-bearing coal and microscopic influence mechanism.

Gas and dust posed a threat to the safe working environment of miners. The key to the effectiveness of coal seam water injection in controlling gas and dust was the wetting of the coal body by water. The gas displacement characteristics were crucial for evaluating the wetting effect of coal. To investigate gas displacement characteristics during the water wetting process of gas-bearing coal, this study employed an experimental equipment of water wetting gas-bearing coal to test the gas displacement quantity under varying gas pressure conditions, and the microscopic influence mechanism was revealed. During the water wetting gas-bearing coal, there was an increase in the accumulated displacement gas quantity corresponding to rising adsorption equilibrium pressures, whereas the accumulated displacement gas rate decreased. Water wetting progressively reduced the system's Helmholtz free energy, reaching a minimum at equilibrium, indicative of a balanced wetting state. The displacement gas quantity curve initially rose linearly, reflecting rapid infiltration, then curved upwards more gradually as gravity and viscosity slowed the process, until reaching a relatively stable state. The curve mirrored the coal's saturation progression. The molecular formula of anthracite was C123H58N2O5. Elemental compositions of carbon, hydrogen, oxygen, and nitrogen matched elemental analysis results. The bridge carbon ratio of this molecular model was aligning with the bridge carbon ratio ascertained from the 13C NMR spectrum analysis. Above the coal-water interface, the relative concentration of water molecules increased with the increase of gas pressure. However, below the coal and water interface, the relative concentration of water molecules increased with the decrease of gas pressures. As the gas pressure increased, the adsorption degree of water molecules weakened, the degree of gas displacement in coal decreased, the diffusion coefficient of methane molecules decreased, the dispersion degree of water molecules increased, the aggregation degree weakened, and the diffusion coefficient of water molecules increased. The study results laid a theoretical foundation for revealing the mechanism of coal seam water injection wetting gas-bearing coal, achieving collaborative gas disaster prevention and pre-wetting dust reduction.

Segmentectomy and wedge resection are equivalent for the treatment of early-stage pulmonary carcinoid tumors: A retrospective cohort study.

Currently, there is no consensus regarding the extent of surgery for stage I pulmonary carcinoid (PC) tumors, which encompass typical carcinoid (TC) and atypical carcinoid (AC) tumors. Sublobar resection includes segmental resection and wedge resection; the former is regarded as a type of anatomical resection that is better suited for tumor treatment. Therefore, it needs to be further verified whether differences exist in the effects of the two surgical methods on the survival time of patients. Propensity score matching (PSM) was used. The primary endpoints were cancer-specific survival (CSS) and overall survival (OS) time. Survival differences were analyzed via the Kaplan-Meier method and the log-rank test. There was no significant difference in survival between the sublobar resection and lobectomy groups after PSM in either the TC or AC tumor groups (all p > 0.05). A total of 1680 patients underwent pulmonary wedge resection (TC: n = 1547, AC: n = 133), and 398 patients underwent segmental resection (TC: n = 365, AC: n = 33). After PSM, there were no statistically significant differences in survival, regardless of whether OS or CSS was considered the primary endpoint (OS: p = 0.337; CSS: p = 0.470). Furthermore, segmental resection did not prolong patient survival time compared with wedge resection in different subgroup analyses on the basis of histology, age, and tumor size (all p > 0.05). Finally, the same results were obtained via multivariate Cox analysis (OS: p = 0.153; HR = 1.21; CSS: p = 0.351, HR = 1.32). Sublobar resection could be considered for patients with early-stage typical or atypical pulmonary carcinoid, provided that a rigorous lymph node evaluation is conducted. If the tumor is distant from the pulmonary hilum, either segmentectomy or wedge resection may be performed depending on the specific location of the tumor and the clinical condition of the patient.

Multidimensional analysis of TMEM132A in pan-cancer: unveiling its potential as a biomarker for treatment response prediction.

Background: TMEM132A is a transmembrane protein that regulates gastric cancer cell malignancy and overall survival in bladder cancer patients. However, while some studies have investigated the involvement of TMEM132A in specific cancers, further systematic studies are required to elucidate its specific mechanisms of action in different cancer types. Methods: We investigated the pan-cancer role of TMEM132A using several databases. We analyzed TMEM132A expression and its correlation with clinical survival, immune checkpoints, tumor stemness score, prognostic value, immunomodulators, genomic profiles, immunological characteristics, immunotherapy and functional enrichment. Results: First, it was observed that TMEM132A expression levels were higher in the majority of tumors compared to non-tumor tissues. In addition, high TMEM132A expression may have a higher prognostic value in some cancers. Furthermore, TMEM132A was significantly associated with immune checkpoints, immunomodulators, prognosis, immunomodulatory genes, tumor stemness score, cell function status and immune infiltration in most tumors. Further analysis of TMEM132A-related gene enrichment, mutation sites and types, RNA modification and genomic heterogeneity showed that the major mutations of TMEM132A were missense mutations and that TMEM132A plays a very important role in UCEC, LUAD and LIHC. Finally, these results suggest that high TMEM132A expression may be associated with a better response to specific immunotherapies. Conclusion: This comprehensive study uncovers an important function for TMEM132A in different types of cancer. It also has the potential to identify TMEM132A as a potential biomarker for predicting treatment response. This may help us to better understand how TMEM132A plays a role in cancer and provide valuable insights for developing personalised treatments.

Multi-Sensor-Assisted Low-Cost Indoor Non-Visual Semantic Map Construction and Localization for Modern Vehicles.

With the transformation and development of the automotive industry, low-cost and seamless indoor and outdoor positioning has become a research hotspot for modern vehicles equipped with in-vehicle infotainment systems, Internet of Vehicles, or other intelligent systems (such as Telematics Box, Autopilot, etc.). This paper analyzes modern vehicles in different configurations and proposes a low-cost, versatile indoor non-visual semantic mapping and localization solution based on low-cost sensors. Firstly, the sliding window-based semantic landmark detection method is designed to identify non-visual semantic landmarks (e.g., entrance/exit, ramp entrance/exit, road node). Then, we construct an indoor non-visual semantic map that includes the vehicle trajectory waypoints, non-visual semantic landmarks, and Wi-Fi fingerprints of RSS features. Furthermore, to estimate the position of modern vehicles in the constructed semantic maps, we proposed a graph-optimized localization method based on landmark matching that exploits the correlation between non-visual semantic landmarks. Finally, field experiments are conducted in two shopping mall scenes with different underground parking layouts to verify the proposed non-visual semantic mapping and localization method. The results show that the proposed method achieves a high accuracy of 98.1% in non-visual semantic landmark detection and a low localization error of 1.31 m.

Brominated Flame Retardants (BFRs) in China Over the Past Half-Century: Stocks, Flows, Fates, and Ecological Risks.

China is a significant producer and consumer of various brominated flame retardants (BFRs), raising environmental concerns due to their widespread presence and potential threats to ecosystems and organisms. This study adopts a life cycle perspective, combining material flow analysis, multimedia environmental modeling, and ecological risk assessment to systematically analyze the substance metabolism and ecological risks of six BFR types in China from 1970 to 2021. The findings reveal that China's cumulative BFR consumption reached 3.3 Mt, with the electronics sector being the predominant contributor at 52.1%. Consequently, 1.5 kt of BFRs were released into the environment, with 24.9%, 31.5%, and 43.6% being discharged into the air, water, and soil, respectively. Notably, the proportion of novel BFRs in emissions has steadily increased over the years, exemplified by the increase in decabromodiphenyl ethane (DBDPE) from 21.3% in 2010 to 30.1% in 2021. Geographically, BFR concentrations are higher in the eastern and southwestern regions compared to those in the northwest. Presently, certain BFRs like tetrabromobisphenol A (TBBPA) and DBDPE exhibit moderate to high ecological risks, primarily concentrated in the Shandong and Sichuan provinces. A combination of efficient recycling, emission control, and substitution with novel flame-retardant can minimize the exposure of BFRs to the environment and organisms.

Time-dependent efficacy analysis of first-line immunotherapies for advanced non-small cell lung cancer.

BACKGROUND: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. METHODS: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. RESULTS: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. CONCLUSIONS: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.

The causal relationship between autoimmune diseases and age-related macular degeneration: A two-sample mendelian randomization study.

OBJECTIVE: The aim of this study is to investigate the potential causal relationship between autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and age-related macular degeneration (AMD). By utilizing the two-sample Mendelian Randomization (MR) approach, we endeavor to address this complex medical issue. METHODS: Genome-wide association study (GWAS) data for autoimmune diseases and AMD were obtained from the IEU Open GWAS database and the FinnGen consortium. A series of stringent SNP filtering steps was applied to ensure the reliability of the genetic instruments. MR analyses were conducted using the TwoSampleMR and MR-PRESSO packages in R. The inverse-variance weighted (IVW) method served as the primary analysis, complemented by multiple supplementary analyses and sensitivity tests. RESULTS: Within the discovery sample, only a statistically significant inverse causal relationship between multiple sclerosis (MS) and AMD was observed (OR = 0.92, 95% CI: 0.88-0.97, P = 0.003). This finding was confirmed in the replication sample (OR = 0.85, 95% CI: 0.80-0.89, P = 3.32×10-12). No statistically significant associations were detected between systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Type 1 diabetes and AMD. CONCLUSION: Strong evidence is provided by this study to support the existence of an inverse causal relationship between multiple sclerosis and age-related macular degeneration. However, no causal evidence was found linking other autoimmune diseases with AMD. These findings not only offer novel insights into the potential etiological mechanisms underlying AMD but also suggest possible directions for future clinical interventions.

Absent in Melanoma 2 Mediates Inflammasome Signaling Activation against Clostridium perfringens Infection.

Absent in melanoma 2 (AIM2), a key component of the IFI20X/IFI16 (PYHIN) protein family, is characterized as a DNA sensor to detect cytosolic bacteria and DNA viruses. However, little is known about its immunological role during pathogenic Clostridium perfringens (C. perfringens) infection, an extracellular bacterial pathogen. In a pathogenic C. perfringens gas gangrene model, Aim2-/- mice are more susceptible to pathogenic C. perfringens soft tissue infection, revealing the importance of AIM2 in host protection. Notably, Aim2 deficiency leads to a defect in bacterial killing and clearance. Our in vivo and in vitro findings further establish that inflammasome signaling is impaired in the absence of Aim2 in response to pathogenic C. perfringens. Mechanistically, inflammasome signaling downstream of active AIM2 promotes pathogen control. Importantly, pathogenic C. perfringens-derived genomic DNA triggers inflammasome signaling activation in an AIM2-dependent manner. Thus, these observations uncover a central role for AIM2 in host defense and triggering innate immunity to combat pathogenic C. perfringens infections.

Development and anatomy of petals with specialized nectar holder and pollen container in Fumarioideae (Papaveraceae).

MAIN CONCLUSION: Petal developmental characteristics in Fumarioideae were similar at early stages, and the specialized nectar holder/pollen container formed by the outer/inner petals. The micro-morphology of these two structures, however, shows diversity in seven species. Elaborate petals have been modified to form different types, including petal lobes, ridges, protuberances, and spurs, each with specialized functions. Nectar holder and pollen container presumably have a function in plant-pollinator interactions. In Fumarioideae, four elaborate petals of the disymmetric/zygomorphic flower present architecture forming the "nectar holder" and "pollen container" structure at the bottom and top separately. In the present study, the petals of seven species in Fumarioideae were investigated by scanning electron microscopy, light microscope, and transmission electron microscopes. The results show that petal development could divided into six stages: initiation, enlargement, adaxial/abaxial differentiation, elaborate specializations (sacs, spurs, and lobes formed), extension, and maturation, while the specialized "nectar holder" and "pollen container" structures mainly formed in stage 4. "Nectar holder" is developed from the shallow sac/spur differentiated at the base of the outer petal, eventually forming a multi-organized complex structure, together with staminal nectaries (1-2) with individual sizes. A semi-closed ellipsoidal "pollen container" is developed from the apical part of the 3-lobed inner petals fused by middle lobes and attain different sizes. The adaxial epidermis cells are specialized, with more distinct punctate/dense columnar protrusions or wavy cuticles presented on obviously thickening cell walls. In addition, a large and well-developed cavity appears between the inner and outer epidermis of the petals. As an exception, Hypecoum erectum middle lobes present stamen mimicry. Elaborate petal structure is crucial for comprehending the petal diversity in Fumarioideae and provides more evidence for further exploration of the reproductive study in Papaveraceae.

Vividness of visual imagery is associated with the effect of relaxation response meditation training in elderly people with nonorganic insomnia: A randomized, double-blind, multi-center clinical trial.

BACKGROUND: This study aims to explore the efficacy of Relaxation Response Meditation Training (RRMT) on elderly individuals with different levels of vividness of visual imagery. METHODS: In this randomized controlled, double-blind, multi-center clinical trial, we recruited a total of 136 elderly individuals who were over 60 years with nonorganic sleep disorders to participate in a 4-week RRMT intervention from October 2020 to October 2022. The intervention occurred twice a week, totaling eight times. These individuals were divided into high and low groups based on the vividness of visual imagery, and then randomly assigned to either the control or intervention groups, as follows: low-visualizers intervention group (LI group); low-visualizers control group (LC group); high-visualizers intervention group (HI group); high-visualizers control group (HC group). Their social and psychological parameters were assessed before and after the intervention by the Pittsburgh Sleep Quality Index (PSQI), the Revised Piper's fatigue scale (RPFS), General well-being scale (GWB), and Satisfaction rating. The alpha waves of patients were also collected through electroencephalogram to assess their level of relaxation. RESULTS: Compared to the LI group, the HI group had a greater reduction rate in the PSQI score [25.2 % (18.8 % to 31.7 %), P < 0∙001], shorter sleep latency (P = 0.001), lower frequency of sleep medication (P < 0.001), lower PSQI scores (P < 0.001), and higher GWB scores (P < 0.001). There were significant differences in all indicators in the HI group vs. HC group and in the LI group vs. LC group. In the first five relaxation training sessions, there was no statistically significant difference in the proportion of α waves between the LI group and the LC group; however, from the sixth session onward, we observed a statistically significant difference (t = 2.86, P = 0.019)，while The HI group and HC group showing significant differences in the first relaxation training session (t = 4.464, P < 0.001). There was a statistically significant difference in subjective satisfaction between the intervention group and the control group (x2 = 49.605, P < 0.001). CONCLUSION: In this study, we found that most elderly people benefitted from RRMT regardless of their vividness of visual imagery. However, low-visualizers experienced slower and less effective results, so these patients may benefit more from alternative approaches.

Preparation and sustained-release of chitosan-alginate bilayer microcapsules containing aromatic compounds with different functional groups.

This study investigated the release of aromatic compounds with distinct functional groups within bilayer microcapsules. Bilayer microcapsules of four distinctive core materials (benzyl alcohol, eugenol, cinnamaldehyde, and benzoic acid) were synthesized via freeze-drying. Chitosan (CS) and sodium alginate (ALG) were used as wall materials. CS concentration, using orthogonal experiments with the loading ratio as a metric. Under optimal conditions, three other types of microcapsules (cinnamic aldehyde, benzoic acid, and benzyl alcohol) were obtained. The four types of microcapsules were characterized using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), and thermogravimetric analysis (TGA), and their sustained release characteristics were evaluated. The optimal conditions were: CS dosage, 1.2 %; CS-to-eugenol mass ratio, 1:2; and CS-to-ALG mass ratio, 1:1. By comparing the IR spectra of the four types of microcapsules, wall material, and core material, the core materials were revealed to be encapsulated within the wall material. SEM results revealed that the granular protuberances on the surface of the microcapsules were closely aligned and persistent when magnified 2000×. The TEM results indicated that all four microcapsules had a spherical and bilayer structure. The thermal stability and sustained release results showed that the four microcapsules were more resilient and less volatile than the four core materials. The release conformed to first-order kinetics, and the release ratios of the four microcapsules were as follows: benzyl alcohol microcapsules Ëƒ eugenol microcapsules Ëƒ cinnamaldehyde microcapsules Ëƒ benzoic acid microcapsules. The prepared bilayer microcapsules encapsulated four different core materials with good sustained release properties.

Graphiumisides A-D, Monoterpene Glycosides from an Animal-Derived Endophytic Fungus Graphium sp. GD-11.

Four new monoterpene rhamnosides, graphiumisides A-D (1-4), along with four known steroid compounds (5-8) were isolated from the fermentation extract of animal-derived endophytic fungus, Graphium sp. GD-11. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HRESIMS spectroscopic analyses, and other spectroscopic methods. Compounds 1-4 exhibit a distinctive structure connected by one p-menthane type monoterpene and one L-rhamnose. This is the first report of monoterpene glycosides from Graphium sp. All compounds (1-8) were tested for cytotoxic activities against four cancer cell lines (HepG2, SMMC7721, SW480, and A549), and only compound 1 showed weak anti-tumor activity against SMMC7721 cells.

Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.

How consistent are the key recommendations, and what is the quality of guidelines and expert consensus regarding paediatric cow's milk protein allergy?

The objective of this study was to assess the quality and consistency of recommendations in clinical practice guidelines (CPGs) and expert consensus on paediatric cow's milk protein allergy (CMPA) to serve as a foundation for future revisions and enhancements of clinical guidelines and consensus documents. We conducted a comprehensive literature search across several databases, including the Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, UpToDate, ClinicalKey, DynaMed Plus and BMJ Best Practice. We spanned the search period from the inception of each database through October 1, 2023. We integrated subject headings (MeSH/Emtree) and keywords into the search strategy, used the search methodologies of existing literature and developed it in collaboration with a librarian. Two trained researchers independently conducted the literature screening and data extraction. We evaluated methodological quality and recommendations by using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and AGREE-Recommendations for Excellence (AGREE-REX) tools. Moreover, we compared and summarized key recommendations from high-quality CPGs. Our study included 27 CPGs and expert consensus documents on CMPA. Only four CPGs (14.8%) achieved a high-quality AGREE II rating. The four high-quality CPGs consistently provided recommendations for CMPA. The highest scoring domains for AGREE II were 'scope and purpose' (77 ± 12%) and 'clarity of presentation' (75 ± 22%). The lowest scoring domains were 'stakeholder involvement' (49 ± 21%), 'rigor of development' (34 ± 20%) and 'applicability' (12 ± 20%). Evaluation with AGREE-REX generally demonstrated low scores across its domains.   Conclusion: Recommendations within high-quality CPGs for the paediatric CMPA showed fundamental consistency. Nevertheless, the methodology and recommendation content of CPGs and the expert consensus exhibited low quality, thus indicating a substantial scope for enhancement. Guideline developers should rigorously follow the AGREE II and AGREE-REX standards in creating CPGs or expert consensuses to guarantee their clinical efficacy in managing paediatric CMPA. What is Known: • The quality of clinical practice guidelines and expert consensus on paediatric cow's milk protein allergy (CMPA) remains uncertain. • There is a lack of clarity regarding the consistency of crucial recommendations for CMPA management. What is New: • Improving the methodological quality of guidelines and consensus on CMPA requires greater emphasis on stakeholder engagement, rigorous development processes, and practical applicability. • The recommendations from four high-quality guidelines align. However, addressing clinical applicability, integrating values and preferences, and ensuring actionable implementation are critical to improving the quality of all guidelines.

Zn-based batteries for sustainable energy storage: strategies and mechanisms.

Batteries play a pivotal role in various electrochemical energy storage systems, functioning as essential components to enhance energy utilization efficiency and expedite the realization of energy and environmental sustainability. Zn-based batteries have attracted increasing attention as a promising alternative to lithium-ion batteries owing to their cost effectiveness, enhanced intrinsic safety, and favorable electrochemical performance. In this context, substantial endeavors have been dedicated to crafting and advancing high-performance Zn-based batteries. However, some challenges, including limited discharging capacity, low operating voltage, low energy density, short cycle life, and complicated energy storage mechanism, need to be addressed in order to render large-scale practical applications. In this review, we comprehensively present recent advances in designing high-performance Zn-based batteries and in elucidating energy storage mechanisms. First, various redox mechanisms in Zn-based batteries are systematically summarized, including insertion-type, conversion-type, coordination-type, and catalysis-type mechanisms. Subsequently, the design strategies aiming at enhancing the electrochemical performance of Zn-based batteries are underscored, focusing on several aspects, including output voltage, capacity, energy density, and cycle life. Finally, challenges and future prospects of Zn-based batteries are discussed.

The Potential of Co-Evolution and Interactions of Gut Bacteria-Phages in Bamboo-Eating Pandas: Insights from Dietary Preference-Based Metagenomic Analysis.

Bacteria and phages are two of the most abundant biological entities in the gut microbiome, and diet and host phylogeny are two of the most critical factors influencing the gut microbiome. A stable gut bacterial community plays a pivotal role in the host's physiological development and immune health. A phage is a virus that directly infects bacteria, and phages' close associations and interactions with bacteria are essential for maintaining the stability of the gut bacterial community and the entire microbial ecosystem. Here, we utilized 99 published metagenomic datasets from 38 mammalian species to investigate the relationship (diversity and composition) and potential interactions between gut bacterial and phage communities and the impact of diet and phylogeny on these communities. Our results highlight the co-evolutionary potential of bacterial-phage interactions within the mammalian gut. We observed a higher alpha diversity in gut bacteria than in phages and identified positive correlations between bacterial and phage compositions. Furthermore, our study revealed the significant influence of diet and phylogeny on mammalian gut bacterial and phage communities. We discovered that the impact of dietary factors on these communities was more pronounced than that of phylogenetic factors at the order level. In contrast, phylogenetic characteristics had a more substantial influence at the family level. The similar omnivorous dietary preference and closer phylogenetic relationship (family Ursidae) may contribute to the similarity of gut bacterial and phage communities between captive giant panda populations (GPCD and GPYA) and omnivorous animals (OC; including Sun bear, brown bear, and Asian black bear). This study employed co-occurrence microbial network analysis to reveal the potential interaction patterns between bacteria and phages. Compared to other mammalian groups (carnivores, herbivores, and omnivores), the gut bacterial and phage communities of bamboo-eating species (giant pandas and red pandas) exhibited a higher level of interaction. Additionally, keystone species and modular analysis showed the potential role of phages in driving and maintaining the interaction patterns between bacteria and phages in captive giant pandas. In sum, gaining a comprehensive understanding of the interaction between the gut microbiota and phages in mammals is of great significance, which is of great value in promoting healthy and sustainable mammals and may provide valuable insights into the conservation of wildlife populations, especially endangered animal species.