Mineralization, degradation and osteogenic property of polylactide multicomponent porous composites for bone repair: In vitro and in vivo study.

Gelatin and hydroxyapatite were assembled into polylactide porous matrix to prepare multicomponent porous composites for bone repair (PLA-gH). PLA-gH possessed a superior ability of mineralization. During simulated body fluids (SBF), the spherical Ca-P depositions on surface of PLA-gH became bulk as Ca/P decreased, while they locally turned into the rod with different variation in Ca/P during SBF containing bovine serum albumin (SBF-BSA), indicating that the mineralization of PLA-gH could be regulated by BSA. Meanwhile, PLA-gH possessed good degradation behaviour, especially in SBF-BSA, the degradation of PLA porous matrix was higher than that in SBF after 14-day immersion, whose crystallinity (Xc) decreased to a slightly lower level. Gelatin and hydroxyapatite endowed PLA-gH with good osteogenic property, characterized by obvious osteogenic differentiation and bone regeneration. In terms of predicting the cytocompatibility, osteogenic differentiation and new bone mineralization of PLA-gH by in vitro methods, applying SBF-BSA may be more reliable than SBF.

V4RIN: visual analysis of regional industry network with domain knowledge.

The regional industry network (RIN) is a type of financial network derived from industry networks that possess the capability to describe the connections between specific industries within a particular region. For most investors and financial analysts lacking extensive experience, the decision-support information provided by industry networks may be too vague. Conversely, RINs express more detailed and specific industry connections both within and outside the region. As RIN analysis is domain-specific and current financial network analysis tools are designed for generalized analytical tasks and cannot be directly applied to RINs, new visual analysis approaches are needed to enhance information exploration efficiency. In this study, we collaborated with domain experts and proposed V4RIN, an interactive visualization analysis system that integrates predefined domain knowledge and data processing methods to support users in uploading custom data. Through multiple views in the system panel, users can comprehensively explore the structure, geographical distribution, and spatiotemporal variations of the RIN. Two case studies were conducted and a set of expert interviews with five domain experts to validate the usability and reliability of our system.

Interpretable baseflow segmentation and prediction based on numerical experiments and deep learning.

Baseflow is a crucial water source in the inland river basins of high-cold mountainous region, playing a significant role in maintaining runoff stability. It is challenging to select the most suitable baseflow separation method in data-scarce high-cold mountainous region and to evaluate effects of climate factors and underlying surface changes on baseflow variability and seasonal distribution characteristics. Here we attempt to address how meteorological factors and underlying surface changes affect baseflow using the Grey Wolf Optimizer Digital Filter Method (GWO-DFM) for rapid baseflow separation and the Long Short-Term Memory (LSTM) neural network model for baseflow prediction, clarifying interpretability of the LSTM model in baseflow forecasting. The proposed method was successfully implemented using a 63-year time series (1958-2020) of flow data from the Tai Lan River (TLR) basin in the high-cold mountainous region, along with 21 years of ERA5-land meteorological data and MODIS data (2000-2020). The results indicate that: (1) GWO-DFM can rapidly identify the optimal filtering parameters. It employs the arithmetic average of three methods, namely Chapman, Chapman-Maxwell and Eckhardt filter, as the best baseflow separation approach for the TLR basin. Additionally, the baseflow significantly increases after the second mutation of the baseflow rate. (2) Baseflow sources are mainly influenced by precipitation infiltration, glacier frozen soil layers, and seasonal ponding. (3) Solar radiation, temperature, precipitation, and NDVI are the primary factors influencing baseflow changes, with Nash-Sutcliffe efficiency coefficients exceeding 0.78 in both the LSTM model training and prediction periods. (4) Changes in baseflow are most influenced by solar radiation, temperature, and NDVI. This study systematically analyzes the changes in baseflow and response mechanisms in high-cold mountainous region, contributing to the management of water resources in mountainous basins under changing environmental conditions.

Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics.

Regulatory T cells (Tregs), a subset of CD4+ T cells, are indispensable in maintaining immune self-tolerance and have been utilized in various diseases. Treg-derived extracellular vesicles (Treg-EVs) have been discovered to play an important role in the mechanism of Treg functions. As cell-derived membranous particles, EVs carry multiple bioactive substances that possess tremendous potential for theranostics. Treg-EVs are involved in numerous physiological and pathological processes, carrying proteins and miRNAs inherited from the parental cells. To comprehensively understand the function of Treg-EVs, here we reviewed the classification of Treg-EVs, the active molecules in Treg-EVs, their various applications in diseases, and the existing challenges for Treg-EVs based theranostics. This Review aims to clarify the feasibility and potential of Treg-EVs in diseases and theranostics, facilitating further research and application of Treg-EVs.

The self-designed reactor to achieve efficient degradation of polyvinyl alcohol under high-pressure and high-temperature conditions.

A huge amount of polyvinyl alcohol (PVA) fabric is abandoned from nuclear power plants every year, the traditional treatment process will occupy land resources and pollute the environment; therefore, a lot of research has been carried out on the chemical treatment of PVA fabric. Herein, the performance of degradation of polyvinyl alcohol under high-pressure and high-temperature conditions is investigated. The effects of the initial pH value, reaction temperature, molar ratio of H2O2/Fe2+, and H2O2 dosage on PVA degradation were evaluated. In the tested ranges in this work, the degradation of PVA fabric via high-pressure and high-temperature method was optimum at the initial pH value of 4, reaction temperature of 300℃, molar ratio of H2O2/Fe2+ as 10, and H2O2 dosage of 13 g/L. The PVA removal rate and TOC removal rate were 99.99% and 97.36%, respectively. Meanwhile, the high-pressure and high-temperature methods also had a great effect on the removal of Rhodamine-B and Reactive Red X-3B, the removal rates of Rhodamine-B and Reactive Red X-3B were 99.83% and 99.76%, respectively. The reaction mechanism of high-pressure and high-temperature methods was also discussed in this study.

Proficiency Development and Learning Curve in Robot-Assisted Spine Surgery Using the ExcelsiusGPS® System: Experience From a Single Institution.

STUDY DESIGN: Retrospective Cohort Study Objectives: Robot-assisted spine surgery (RASS) is a rapidly evolving technique with potential benefits for improving surgical outcomes. A number of studies on RASS learning curve have focused on early iterations of the Mazor robot. Limited research exists on the learning curve associated with using the Globus Medical ExcelsiusGPS® system. In this retrospective study, we aimed to evaluate the learning curve of RASS using the ExcelsiusGPS® system at a single institution. METHODS: A total of 95 patients (541 screws) who underwent RASS between 2021 and 2022 were included. Variables including operative time, robot registration time, screw placement time, fluoroscopy utilization, and complications were analyzed. Statistical analysis was performed using descriptive statistics and two-sample t-tests. RESULTS: The average operative time significantly decreased after the first 14 cases, indicating a learning curve. However, no significant improvement was observed in robot registration time. Notably, screw placement time significantly improved after approximately 13 cases. When controlling for the number of levels fused, the trends remained consistent. CONCLUSIONS: Our study confirmed the presence of a learning curve in RASS using the ExcelsiusGPS® system and demonstrated rapid proficiency development. Our findings highlight the relatively quick learning curve of 1 RASS system.

Population genomics analysis reveals footprints of selective breeding in a rapid-growth variety of Paulownia fortunei with apical dominance.

Paulownia fortunei is an ecologically and economically valuable tree cultivated for its rapid growth and high-quality timber. To enhance Paulownia germplasm, we have developed the elite variety QingT with patented advantages in growth rate and apical dominance. To illuminate the genetic basis of QingT's superior traits, here we harness comparative population genomics to analyze genomic variation patterns between QingT and common Paulownia. We performed whole-genome re-sequencing of 30 QingT and 30 common samples, detecting 15.6 million SNPs and 2.6 million indels. Phylogeny and population structure analyses robustly partitioned common and QingT into distinct groups which indicate robust genome stabilization. QingT exhibited reduced heterozygosity and linkage disequilibrium decay compared to common Paulownia, reflecting high recombination, indicating hybridizing effects with common white-flowered string is the source of its patented advantages. Genome selection scans uncovered 25 regions of 169 genes with elevated nucleotide diversity, indicating selection sweeps among groups. Functional analysis of sweep genes revealed upregulation of ribosomal, biosynthesis, and growth pathways in QingT, implicating enhanced protein production and developmental processes in its rapid growth phenotype. This study's insights comprehensively chart genomic variation during Paulownia breeding, localizing candidate loci governing agronomic traits, and underpinnings of future molecular breeding efforts to boost productivity.

Wastewater-based estimation of diabetes mellitus prevalence in 237 cities: A cross-China study.

Diabetes mellitus, a metabolic disease characterized by hyperglycemia, has been witnessed as a rapidly escalating worldwide health crisis. China currently had 140.9 million diabetic population in 2021, which was the largest globally. DM has witnessed a significant surge in the past few decades, leading to an alarming rise in the overall burden caused by this disease. To monitor the near real-time DM prevalence and the consumption of first-line anti-diabetic drugs, a wastewater-based epidemiology (WBE) approach based on the back-calculation of metformin concentration was implemented in 237 cities in China. The quantitative analysis of metformin in wastewater was conducted by LC-MS/MS with satisfactory results of method validation. The average concentration of metformin in wastewater was 14.07 ± 13.16 µg/L, and the per capita consumption was 5.16 ± 2.08 mg/day/inh, ranging from 0.90 to 10.36 ± 4.63 mg/day/inh. The calculated metformin prevalence was found to be 0.52 % ± 0.28 %, and the final estimated DM prevalence was 11.33 % ± 4.99 %, which was nearly consistent with the result of the International Diabetes Federation survey of 9.98 %. The results suggested that metformin might be one of the suitable WBE biomarkers in DM monitoring and WBE strategy could potentially enable the estimation of DM prevalence in most of Chinese cities after reasonable correction of associated parameters.

Therapeutic effects and molecular mechanisms of quercetin in gynecological disorders.

Quercetin is a representative flavonoid that is widely present in fruits, herbs, and vegetables. It is also an important active core component in traditional Chinese medicines. As an important flavonoid, quercetin has various properties and exerts antioxidant, anti-inflammatory, and cardioprotective effects. The public interest in quercetin is increasing, and quercetin has been used to prevent or treat numerous of diseases, such as polycystic ovary syndrome (PCOS), cancer, autoimmune diseases and chronic cardiovascular diseases, in clinical experiments and animal studies due to its powerful antioxidant properties and minimal side effects. Quercetin exerts marked pharmacological effects on gynecological disorders; however, there have been no reviews about the potential health benefits of quercetin in the context of gynecological disorders, including PCOS, premature ovary failure (POF), endometriosis (EM), ovarian cancer (OC), cervical cancer (CC) and endometrial carcinoma (EC). Thus, this review aimed to summarize the biological effects of quercetin on gynecological disorders and its mechanisms.

Estimation of the spatial pattern of gout prevalence across China by wastewater-based epidemiology.

Gout is a metabolic arthritis caused by hyperuricemia. In recent years, the prevalence of gout has been increased significantly in China due to the improvement of the living standards, and gout has become another common metabolic disease following diabetes mellitus. Gout severely affects the health status and life quality of human. In order to monitor the near real-time prevalence of gout, a wastewater-based epidemiology (WBE) approach was carried out in 257 Chinese cities using febuxostat as the biomarker. Febuxostat in wastewater was measured by a LC-MS/MS method with satisfactory results of method validation. The average concentration of febuxostat in wastewater was 53.05 ± 31.76 ng/L, with the estimated per capita consumption of 124.40 ± 73.37 mg/day/1000 inhabitant. The calculated prevalence of febuxostat was 0.41 % ± 0.24 %, and the prevalence of gout was finally estimated to be 1.30 % ± 0.77 % (0.60 % to 2.11 %), which was nearly consistent with value of 1.10 % obtained from the Guideline for the diagnosis and management of hyperuricemia and gout in China (2019). The results indicated that the febuxostat-based WBE approach might be reasonable to assess the near real-time gout prevalence in China.

A novel correction method for modelling parameter-driven autocorrelated time series with count outcome.

BACKGROUND: Count time series (e.g., daily deaths) are a very common type of data in environmental health research. The series is generally autocorrelated, while the widely used generalized linear model is based on the assumption of independent outcomes. None of the existing methods for modelling parameter-driven count time series can obtain consistent and reliable standard error of parameter estimates, causing potential inflation of type I error rate. METHODS: We proposed a new maximum significant ρ correction (MSRC) method that utilizes information of significant autocorrelation coefficient ρ estimate within 5 orders by moment estimation. A Monte Carlo simulation was conducted to evaluate and compare the finite sample performance of the MSRC and classical unbiased correction (UB-corrected) method. We demonstrated a real-data analysis for assessing the effect of drunk driving regulations on the incidence of road traffic injuries (RTIs) using MSRC in Shenzhen, China. Moreover, there is no previous paper assessing the time-varying intervention effect and considering autocorrelation based on daily data of RTIs. RESULTS: Both methods had a small bias in the regression coefficients. The autocorrelation coefficient estimated by UB-corrected is slightly underestimated at high autocorrelation (≥ 0.6), leading to the inflation of the type I error rate. The new method well controlled the type I error rate when the sample size reached 340. Moreover, the power of MSRC increased with increasing sample size and effect size and decreasing nuisance parameters, and it approached UB-corrected when ρ was small (≤ 0.4), but became more reliable as autocorrelation increased further. The daily data of RTIs exhibited significant autocorrelation after controlling for potential confounding, and therefore the MSRC was preferable to the UB-corrected. The intervention contributed to a decrease in the incidence of RTIs by 8.34% (95% CI, -5.69-20.51%), 45.07% (95% CI, 25.86-59.30%) and 42.94% (95% CI, 9.56-64.00%) at 1, 3 and 5 years after the implementation of the intervention, respectively. CONCLUSIONS: The proposed MSRC method provides a reliable and consistent approach for modelling parameter-driven time series with autocorrelated count data. It offers improved estimation compared to existing methods. The strict drunk driving regulations can reduce the risk of RTIs.

Regulatory T cell-derived exosome mediated macrophages polarization for osteogenic differentiation in fracture repair.

Refractory fracture presents an intractable challenge in trauma treatment. Selective polarization of macrophages as well as the recruitment of osteogenic precursor cells play key roles in osteogenic differentiation during fracture healing. Here we constructed regulatory T cell (Treg)-derived exosomes (Treg-Exo) for the treatment of fracture. The obtained exosomes displayed a spheroid shape with a hydrated particle size of approximately 130 nm. With further purification using CD39 and CD73 antibody-modified microfluidic chips, CD39 and CD73 specifically expressing exosomes were obtained. This kind of Treg-Exo utilized the ectonucleotidases of CD39 and CD73 to catalyze the high level of ATP in the fracture area into adenosine. The generated adenosine further promoted the selective polarization of macrophages. When interacting with mesenchymal stem cells (MSCs, osteogenic precursor cells), both Treg-Exo and Treg-Exo primed macrophages facilitated the proliferation and differentiation of MSCs. After administration in vivo, Treg-Exo effectively promoted fracture healing compared with conventional T cell-derived exosome. To further improve the delivery efficacy of exosomes and integrate multiple biological processes of fracture healing, an injectable hydrogel was fabricated to co-deliver Treg-Exo and stromal cell-derived factor 1 alpha (SDF-1α). With the dual effect of Treg-Exo for macrophage polarization and SDF-1α for MSC recruitment, the multifunctional hydrogel exerted a synergistic effect on fracture repair acceleration. This study provided a promising therapeutic candidate and synergistic strategy for the clinical treatment of fracture.

Three-dimensional printing of wood.

Natural wood has served as a foundational material for buildings, furniture, and architectural structures for millennia, typically shaped through subtractive manufacturing techniques. However, this process often generates substantial wood waste, leading to material inefficiency and increased production costs. A potential opportunity arises if complex wood structures can be created through additive processes. Here, we demonstrate an additive-free, water-based ink made of lignin and cellulose, the primary building blocks of natural wood, that can be used to three-dimensional (3D) print architecturally designed wood structures via direct ink writing. The resulting printed structures, after heat treatment, closely resemble the visual, textural, olfactory, and macro-anisotropic properties, including mechanical properties, of natural wood. Our results pave the way for 3D-printed wooden construction with a sustainable pathway to upcycle/recycle natural wood.

A distinct "repair" role of regulatory T cells in fracture healing.

Regulatory T cells (Tregs) suppress immune responses and inflammation. Here, we described the distinct nonimmunological role of Tregs in fracture healing. The recruitment from the circulation pool, peripheral induction, and local expansion rapidly enriched Tregs in the injured bone. The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs. Punctual depletion of Tregs compromised the fracture healing process, which leads to increased bone nonunion. In addition, bone callus Tregs showed unique T-cell receptor repertoires. Amphiregulin was the most overexpressed protein in bone callus Tregs, and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways. The results of loss- and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction. Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells. Our findings indicate the distinct and nonredundant role of Tregs in fracture healing, which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

Alfalfa MsbHLH115 confers tolerance to cadmium stress through activating the iron deficiency response in Arabidopsis thaliana.

Cadmium (Cd) pollution severely affects plant growth and development, posing risks to human health throughout the food chain. Improved iron (Fe) nutrients could mitigate Cd toxicity in plants, but the regulatory network involving Cd and Fe interplay remains unresolved. Here, a transcription factor gene of alfalfa, MsbHLH115 was verified to respond to iron deficiency and Cd stress. Overexpression of MsbHLH115 enhanced tolerance to Cd stress, showing better growth and less ROS accumulation in Arabidopsis thaliana. Overexpression of MsbHLH115 significantly enhanced Fe and Zn accumulation and did not affect Cd, Mn, and Cu concentration in Arabidopsis. Further investigations revealed that MsbHLH115 up-regulated iron homeostasis regulation genes, ROS-related genes, and metal chelation and detoxification genes, contributing to attenuating Cd toxicity. Y1H, EMSA, and LUC assays confirmed the physical interaction between MsbHLH115 and E-box, which is present in the promoter regions of most of the above-mentioned iron homeostasis regulatory genes. The transient expression experiment showed that MsbHLH115 interacted with MsbHLH121pro. The results suggest that MsbHLH115 may directly regulate the iron-deficiency response system and indirectly regulate the metal detoxification response mechanism, thereby enhancing plant Cd tolerance. In summary, enhancing iron accumulation through transcription factor regulation holds promise for improving plant tolerance to Cd toxicity, and MsbHLH115 is a potential candidate for addressing Cd toxicity issues.

Air-Stable Self-Driven UV Photodetectors on Controllable Lead-Free CsCu2I3 Microwire Arrays.

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

The Effectiveness of National Expanded Program on Immunization With Hepatitis A Vaccines in the Chinese Mainland: Interrupted Time-Series Analysis.

BACKGROUND: The high prevalence of hepatitis A delivered a blow to public health decades ago. The World Health Organization (WHO) set a goal to eliminate viral hepatitis including hepatitis A by 2030. In 2008, hepatitis A vaccines were integrated into the Expanded Program on Immunization (EPI) in China to alleviate the burden of hepatitis A, although the effectiveness of the EPI has not been well investigated. OBJECTIVE: We aimed to evaluate the intervention effect at both provincial and national levels on the incidence of hepatitis A in the Chinese mainland from 2005 to 2019. METHODS: Based on the monthly reported number of hepatitis A cases from 2005 to 2019 in each provincial-level administrative division, we adopted generalized additive models with an interrupted time-series design to estimate province-specific effects of the EPI on the incidence of hepatitis A among the target population (children aged 2-9 years) from 2005 to 2019. We then pooled province-specific effect estimates using random-effects meta-analyses. We also assessed the effect among the nontarget population and the whole population. RESULTS: A total of 98,275 hepatitis A cases among children aged 2-9 years were reported in the Chinese mainland from 2005 to 2019, with an average annual incidence of 5.33 cases per 100,000 persons. Nationally, the EPI decreased the hepatitis A incidence by 80.77% (excess risk [ER] -80.77%, 95% CI -85.86% to -72.92%) during the study period, guarding an annual average of 28.52 (95% empirical CI [eCI] 27.37-29.00) cases per 100,000 persons among the target children against hepatitis A. Western China saw a more significant effect of the EPI on the decrease in the incidence of hepatitis A among the target children. A greater number of target children were protected from onset in Northwest and Southwest China, with an excess incidence rate of -129.72 (95% eCI -135.67 to -117.86) and -66.61 (95% eCI -67.63 to -64.22) cases per 100,000 persons on average, respectively. Intervention effects among nontarget (ER -32.88%, 95% CI -39.76% to -25.21%) and whole populations (ER -31.97%, 95% CI -39.61% to -23.37%) were relatively small. CONCLUSIONS: The EPI has presented a lasting positive effect on the containment of hepatitis A in the target population in China. The EPI's effect on the target children also provided a degree of indirect protection for unvaccinated individuals. The continuous surveillance of hepatitis A and the maintenance of mass vaccination should shore up the accomplishment in the decline of hepatitis A incidence to ultimately achieve the goal set by the WHO.

Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial.

BACKGROUND: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea. OBJECTIVE: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval. MAIN OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms. RESULTS: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05). CONCLUSION: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38.

Nano-energy interference: A novel strategy for blunting tumor adaptation and metastasis.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch.

Pain is one of the most common clinical symptoms of cancer patients, seriously affecting the quality of life of patients and bringing heavy mental and economic burden to families and society. The treatment of cancer pain in China is facing numerous challenges, one of which includes the irrational usage of analgesic drugs in clinical practice. As a strong opioid analgesic, transdermal fentanyl patch has been widely used due to its convenient clinical application and obvious therapeutic effect. Several basic-level hospitals and even general hospitals in China fail to appropriate the application of drugs in clinical application due to the lack of understanding of the pharmacological characteristics and clinical application of fentanyl transdermal patch by medical staff, seriously affecting the treatment quality. Therefore, it is imperative to strengthen the rational use and management of fentanyl transdermal patches. Accordingly, the initiation by the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association launched the compilation of the "Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch" (from now on referred to as the "Guidelines") in Hubei Province, China. The experts in the preparation group are experts in many disciplines, such as medicine, pharmacy, and nursing. The expert group determines the outline, prepares the required regulations, and revises it repeatedly. Moreover, these experts put forward suggestions for revision to strictly control the accuracy and scientific authenticity of the contents of the "Guide". Finally, all experts of the preparation team certify and finalize the draft. This "Guide" prepared by experts of the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association and the expert advisory group with joint efforts, aims to play a positive role in promoting the rational clinical use of fentanyl transdermal patch, reducing the mental and economic burden of patients, and ensuring medical quality and medical safety.