The association between thyroid disease and hearing loss: a meta-analysis.

BACKGROUND: It has been shown that there is a link between thyroid-related diseases and hearing loss. OBJECTIVES: The purpose of this study is to investigate the relationship between thyroid-related diseases and hearing loss by conducting a meta-analysis. MATERIAL AND METHODS: A thorough search was carried out in the following electronic databases: PubMed, Cochrane Library, Embase, Web of Science, Google Scholar, Semantic Scholar, and ResearchRabbit. The chi-square test and the I2 index examined the research's heterogeneity. A funnel plot and the Eger test were used to examine publication-biased effects. RESULTS: A total of 48,507 individuals (6482 hypothyroid patients, 4162 hearing loss patients, and 37863 controls) were included in this meta-analysis of 18 research. Individuals with hypothyroidism had a 1.69-fold increased risk of hearing loss compared to those without the condition (OR: 1.69; 95% CI: 1.11-2.57, p < 0.001). among hypothyroidism, the prevalence of hearing loss was 24% (EC: 0.24; 95% CI: 0.11-0.39, p = 0.00), while among hearing-impaired individuals, the prevalence of hypothyroidism was 7% (EC: 0.21; 95% CI: 0.07-0.40). CONCLUSION: This study demonstrated how thyroid dysfunction can raise the chance of hearing loss. To completely comprehend the underlying mechanisms and create efficient treatments for this illness, more study is required.

Sustained therapeutic effects of self-assembled hyaluronic acid nanoparticles loaded with α-Ketoglutarate in various osteoarthritis stages.

Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.

Highly sensitive ECL detection of miRNA based on self-generated coreactant and target-induced catalyzed hairpin assembly.

BACKGROUND: Recently, various techniques have been developed to accurately and sensitively detect tumor biomarkers for the early diagnosis and effective therapy of cancer. The electrochemiluminescence (ECL) method holding outstanding features including high sensitivity, ease of operation, and spatiotemporal controllability exhibited great potential for DNA/RNA detection, immunoassay, cancer cell detection, and environmental analysis. However, a glaring problem of ECL approaches is that the layer-by-layer modification on the electrode leads to poor stability and sensitivity of the sensors. Therefore, new simple and efficient methods for electrode modification which can effectively improve the ECL signal have attracted more and more research interests. RESULTS: Based on the dual amplification strategy of target-induced CHA and nanocomposite probes leading to self-generated co-reactant (H2O2), we proposed a highly sensitive miRNA-ECL detection system. The introduction of the target miRNA-21 triggers the CHA cycle amplification of DNA1 and biotin-modified DNA2, releasing the target miRNA-21 sequence for the target cycle reaction. After the reaction, the newly introduced DNA2 was combined with Au NPs modified with SA and Glucose oxidase (GOD). In the presence of oxygen, glucose was decomposed by GOD to produce H2O2, and then H2O2 was immediately catalyzed by the Hemin/G-quadruplex at the double-stranded end of the CHA product to produce a large amount of O2-•. As a co-reactant of luminol, the ECL signal was significantly enhanced, thereby achieving highly sensitive detection of miRNA-21 content and obtaining a low detection limit of 0.65 fM. The high specificity of the ECL biosensor was also proved by base mismatch. SIGNIFICANCE: Compared with other current detection methods, this sensor can achieve quantitative analysis of other target analytes by flexibly changing the probe DNA sequence, and provide a new feasible solution for the detection of tumor-associated markers. Benefiting from the improved sensitivity and selectivity, the proposed biosensing platform is expected to provide a new strategy for biomarkers analysis and outstanding prospect for further clinical application.

Schwann cell-derived exosomes ameliorate peripheral neuropathy induced by ablation of dicer in Schwann cells.

Background: MicroRNAs (miRNAs) in Schwann cells (SCs) mediate peripheral nerve function. Ablating Dicer, a key gene in miRNA biogenesis, in SCs causes peripheral neuropathy. Exosomes from healthy SCs (SC-Exo) ameliorate diabetic peripheral neuropathy in part via miRNAs. Thus, using transgenic mice with conditional and inducible ablation of Dicer in proteolipid protein (PLP) expressing SCs (PLP-cKO), we examined whether SC-Exo could reduce peripheral neuropathy in PLP-cKO mice. Methods: PLP-cKO mice at the age of 16 weeks (8 week post-Tamoxifen) were randomly treated with SC-Exo or saline weekly for 8 weeks. Age-and sex-matched wild-type (WT) littermates were used as controls. Peripheral neurological functions, sciatic nerve integrity, and myelination were analyzed. Quantitative RT-PCR and Western blot analyses were performed to examine miRNA and protein expression in sciatic nerve tissues, respectively. Results: Compared to the WT mice, PLP-cKO mice exhibited a significant decrease in motor and sensory conduction velocities, thermal sensitivity, and motor coordination. PLP-cKO mice exhibited substantial demyelination and axonal damage of the sciatic nerve. Treatment of PLP-cKO mice with SC-Exo significantly ameliorated the peripheral neuropathy and sciatic nerve damage. PLP-cKO mice showed a substantial reduction in a set of Dicer-related miRNAs known to regulate myelination, axonal integrity, and inflammation such as miR-138, -146a and - 338 in the sciatic nerve. In addition, PLP-cKO mice exhibited significant reduction of myelin forming proteins, early growth response 2 (EGR2) and sex determining region Y-box10 (Sox10), but significantly increased myelination inhibitors, Notch1, c-Jun, and Sox2 and the axonal growth inhibitor phosphatase and tens in homolog (PTEN). However, SC-Exo treatment reversed the PLP-cKO altered miRNAs and proteins. Conclusion: This study demonstrates that exogenous SC-Exo ameliorate peripheral neuropathy induced by Dicer ablation in PLP expressing SCs. The therapeutic benefit may be mediated by the SC-Exo altered miRNAs and their targeted genes.

Design and decoration of copper nanoparticles into lignosulfonate-starch bionanocomposite: Characterization and evaluation of its therapeutic properties on burn wound.

In this report, eco-friendly synthesis for the production of copper nanoparticles by employing the sodium lignosulfonate (NaLS) mixed starch composite (NaLS-Starch/Cu NPs). NaLS-Starch mixed hydrogel has notable reducing and stabilizing potential for preparation of Cu nanoparticles. Characterization of NaLS-Starch/Cu NPs bionanocomposite was subjected to analysis of spectroscopic and microscopic techniques, including FE-SEM, TEM, EDS-elemental mapping, particle size distribution, XRD and ICP. TEM images displayed the spherical structured NaLS-Starch/Cu NPs, averaging 5-10 nm size. NaLS-Starch/Cu NPs were applied to cure the induced burn wounds in 60 Wistar rats. A group was considered as control group. The animals were treated with basal, tetracycline 3 % and NaLS-Starch/Cu NPs 3 % for 30 days and the treatment efficacy was determined according to the burn wound area reduction and molecular and histological characteristics. Taken together, these results support therapeutic use of NaLS-Starch/Cu NPs as potent ointment that may be proposed for burn wound healing. NaLS-Starch/Cu NPs ointment increased the levels of platelet-derived growth factors (PDGF) and fibroblast growth factor (bFGF). The mean wound surface, in all groups treated by NaLS-Starch/Cu NPs was larger than control group.

Construction of a nomogram with IrAE and clinic character to predict the survival of advanced G/GEJ adenocarcinoma patients undergoing anti-PD-1 treatment.

Objective: This study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors. Method: A dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model. Results: After consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model's accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients. Conclusion: This study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

Dual amplification dynamic DNA network system for CRISPR/Cas12a based p53 gene detection.

BACKGROUND: It is estimated that over 50 % of human cancers are caused by mutations in the p53 gene. Early sensitive and accurate detection of the p53 gene is important for diagnosis of cancers in the early stage. However, conventional detection techniques often suffer from strict reaction conditions, or unsatisfied sensitivity, so we need to develop a new strategy for accurate detection of p53 gene with smart designability, multiple signal amplification in mild reaction conditions. RESULTS: In this study, CRISPR/Cas system is exploited in entropy-driven catalysis (EDC) and hybridization chain reaction (CHA) dual signal amplification sensing strategies. The products of both reactions can efficiently and separately activate CRISPR/Cas12a which greatly amplifies the fluorescent signal. The method has good linearity in p53 detection with the concentration ranged from 0.1 fM to 0.5 pM with ultra-low detection limit of 0.096 fM. It also showed good performance in serum, offering potentials for early disease detection. SIGNIFICANCE: The designed dual amplification dynamic DNA network system exhibits an ultra-sensitive fluorescence biosensing for p53 gene identification. The method is simple to operate and requires only one buffer for the experiment, and meanwhile shows smart designability which could be used for a wide range of markers. Thus, we believe the present work will provide a potential tool for the construction and development of sensitive fluorescent biosensors for diseases.

A two-stage maintenance trial of cetuximab-based treatment in RAS and BRAF wild-type unresectable metastatic colorectal cancer: a retrospective real-world study.

Background: To investigate the effectiveness and safety of maintenance regimens based on cetuximab, we conducted a real-world, single-arm, retrospective study at a single center. Methods: In Fujian Medical University Union Hospital, patients with unresectable metastatic colorectal cancer (mCRC) who received cetuximab-based maintenance therapy between December 2020 and December 2021 were included. All patients had RAS and BRAF wild-type. The maintenance regimen consisted of 6-12 cycles of cetuximab plus irinotecan (Phase 1) and cetuximab (Phase 2). Patients could receive reintroduction therapy in case of disease progression during Phase 2. Progression-free survival (PFS), overall survival (OS), and safety data were collected. Results: According to the inclusion and exclusion criteria of the study, a total of 108 subjects who received maintenance therapy were included- 51 experienced disease progression during Phase 1, with PFS (1) of 7.3 months. Among the 52 patients who entered Phase 2, 17 were still in this phase at the end of follow-up, with PFS (2) of 10.1 months. In Phase 2, 35 patients experienced disease progression, of whom 24 received reintroduction therapy, with PFS (3) of 6.7 months. The overall PFS (total) during the maintenance period was 11.9 months, and the OS was 39.2 months. Grade III or higher adverse events were 4.6% during Phase 1 and 0% during Phase 2. Conclusion: Innovative cetuximab-based maintenance therapy showed a trend toward improving the prognosis of mCRC patients with RAS and BRAF wild-type, while the toxic side effects of maintenance therapy were manageable. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2000040940.

Novel nomogram and risk stratification for peritoneal recurrence after curative resection in gastric cancer.

Peritoneal recurrence (PR) in gastric cancer after curative resection has poor prognosis. Therefore, we aimed to construct a nomogram to predict PR, and establish PR score for risk stratification to guide adjuvant chemotherapy. A total of 315 patients with gastric cancer after radical surgery were included, and randomly stratified into training group (n = 221) and validation group (n = 94). Univariate and multivariate analyses were used to determine predictive factors of PR. The nomogram was constructed to predict the risk of PR. We utilized the time-dependent area under the receiver operating characteristic (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA) to evaluate the performance of the nomogram. Multivariate analysis showed that tumor site, N stage, preoperative CEA, and postoperative CA199 were independent predictors of PR. A nomogram was constructed to predict PR based on these factors. The AUC value was 0.755 in the training group and 0.715 in the validation group. The calibration curves showed good agreement between prediction and observation in the training and validation groups. The decision curve analysis displayed a good net benefit of the nomogram. The novel PR score was developed and patients were stratified into the low-, medium-, and high -risk groups. For the high-risk group, postoperative adjuvant chemotherapy significantly improved patients' overall survival (OS) and disease-free survival (DFS). The establishment of nomogram facilitates the prediction of PR after radical gastrectomy, and a novel PR score may help guide adjuvant chemotherapy for gastric cancer.

Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network meta-analysis.

BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Paravertebrally-Injected Multifunctional Hydrogel for Sustained Anti-Inflammation and Pain Relief in Lumbar Disc Herniation.

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.

Does the novel artificial cervical joint complex resolve the conflict between stability and mobility after anterior cervical surgery? a finite element study.

Background and objective: Our group has developed a novel artificial cervical joint complex (ACJC) as a motion preservation instrument for cervical corpectomy procedures. Through finite element analysis (FEA), this study aims to assess this prosthesis's mobility and stability in the context of physiological reconstruction of the cervical spine. Materials and methods: A finite element (FE)model of the subaxial cervical spine (C3-C7) was established and validated. ACJC arthroplasty, anterior cervical corpectomy and fusion (ACCF), and two-level cervical disc arthroplasty (CDA) were performed at C4-C6. Range of motion (ROM), intervertebral disc pressure (IDP), facet joint stress (FJS), and maximum von Mises stress on the prosthesis and vertebrae during loading were compared. Results: Compared to the intact model, the ROM in all three surgical groups demonstrated a decline, with the ACCF group exhibiting the most significant mobility loss, and the highest compensatory motion in adjacent segments. ACJC and artificial cervical disc prosthesis (ACDP) well-preserved cervical mobility. In the ACCF model, IDP and FJS in adjacent segments increased notably, whereas the index segments experienced the most significant FJS elevation in the CDA model. The ROM, IDP, and FJS in both index and adjacent segments of the ACJC model were intermediate between the other two. Stress distribution of ACCF instruments and ACJC prosthesis during the loading process was more dispersed, resulting in less impact on the adjacent vertebrae than in the CDA model. Conclusion: The biomechanical properties of the novel ACJC were comparable to the ACCF in constructing postoperative stability and equally preserved physiological mobility of the cervical spine as CDA without much impact on adjacent segments and facet joints. Thus, the novel ACJC effectively balanced postoperative stability with cervical motion preservation.

In vivo study of a novel 3D-printed motion-preservation artificial cervical corpectomy construct: short-term imaging and biocompatibility evaluations in a goat model.

BACKGROUND: Nonfusion technologies, such as motion-preservation devices, have begun a new era of treatment options in spine surgery. Motion-preservation approaches mainly include total disc replacement for anterior cervical discectomy and fusion. However, for multisegment fusion, such as anterior cervical corpectomy and fusion, the options are more limited. Therefore, we designed a novel 3D-printed motion-preservation artificial cervical corpectomy construct (ACCC) for multisegment fusion. The aim of this study was to explore the feasibility of ACCC in a goat model. METHODS: Goats were treated with anterior C3 corpectomy and ACCC implantation and randomly divided into two groups evaluated at 3 or 6 months. Radiography, 3D CT reconstruction and MRI evaluations were performed. Biocompatibility was evaluated using micro-CT and histology. RESULTS: Postoperatively, all goats were in good condition, with free neck movement. Implant positioning was optimal. The relationship between facet joints was stable. The range of motion of the C2-C4 segments during flexion-extension at 3 and 6 months postoperatively was 7.8° and 7.3°, respectively. The implants were wrapped by new bone tissue, which had grown into the porous structure. Cartilage tissue, ossification centres, new blood vessels, and bone mineralization were observed at the porous metal vertebrae-bone interface and in the metal pores. CONCLUSIONS: The ACCC provided stabilization while preserving the motion of the functional spinal unit and promoting bone regeneration and vascularization. In this study, the ACCC was used for anterior cervical corpectomy and fusion (ACCF) in a goat model. We hope that this study will propel further research of motion-preservation devices.

A triple read-out visible biosensing platform based on multifunctional nanozyme and bipolar electrode for multi-mode detection and imaging of CEA.

In this paper, a proposal of closed bipolar electrode (BPE) and nanozyme based multi-mode biosensing platform is first presented. As a novel integrated chip, multi-mode-BPE (MMBPE) combines enzyme-linked immunoassay (ELISA), electrochemiluminescence (ECL), ECL imaging and light emitting diode (LED) imaging, enabling highly sensitive triple read-out visible detection of cancer embryonic antigen (CEA). The ECL probe Ab2@Au@Co3O4/CoFe2O4 hollow nanocubes (HNCs) with excellent peroxidase (POD) activity is introduced into the BPE cathode through immune adsorption. The Au@Co3O4/CoFe2O4 HNCs can increase the rate of hydrogen peroxide oxidation of TMB, thus promoting the reaction, and can be used for ELISA detection of CEA at different concentrations. The modification of the BPE sensing interface and reporting interface involved the introduction of the luminescent reagent Ru(bpy)32+ to the BPE anode. The decomposition rate of H2O2 increased under the catalytic action of Au@Co3O4/CoFe2O4 HNCs nanozyme, leading to an accelerated electron transfer rate in the MMBPE system and an enhanced ECL signal from Ru(bpy)32+. The LED imaging technology further provides a convenient and visible approach for CEA imaging in which no additional chemicals are needed. The integration of nanoenzymes as the catalytic core in MMBPE system provides impetus, while the combination of nanozymes with BPE expands the application of nanoenzymes in the field of biological analysis. The integration of intelligent chips with multiple modes of detection shows portable, miniaturized, and integrated excellent properties which meets the requirements of modern detection devices and thus offers a flexible approach for determination of nucleic acids, proteins, and cells.

Simultaneously improved photoluminescence, stability, and carrier transport of perovskite nanocrystals by post-synthetic perfluorobutanesulfonic acid treatment.

We report a post-synthetic treatment method based on perfluorobutanesulfonic acid (PFBA) to ameliorate the photophysical performance of perovskite nanocrystals. By virtue of the PFBA treatment, both the photoluminescence efficiency and stability of perovskite quantum dot-based colloidal solutions and the electrical conductivity of their close-packed films are simultaneously improved.

Curcumin-Loaded RH60/F127 Mixed Micelles: Characterization, Biopharmaceutical Characters and Anti-Inflammatory Modulation of Airway Inflammation.

Curcumin's ability to impact chronic inflammatory conditions, such as metabolic syndrome and arthritis, has been widely researched; however, its poor bioavailability limits its clinical application. The present study is focused on the development of curcumin-loaded polymeric nanomicelles as a drug delivery system with anti-inflammatory effects. Curcumin was loaded in PEG-60 hydrogenated castor oil and puronic F127 mixed nanomicelles (Cur-RH60/F127-MMs). Cur-RH60/F127-MMs was prepared using the thin film dispersion method. The morphology and releasing characteristics of nanomicelles were evaluated. The uptake and permeability of Cur-RH60/F127-MMs were investigated using RAW264.7 and Caco-2 cells, and their bioavailability and in vivo/vitro anti-inflammatory activity were also evaluated. The results showed that Cur-RH60/F127-MMs have regular sphericity, possess an average diameter smaller than 20 nm, and high encapsulation efficiency for curcumin (89.43%). Cur-RH60/F127-MMs significantly increased the cumulative release of curcumin in vitro and uptake by cells (p < 0.01). The oral bioavailability of Cur-RH60/F127-MMs was much higher than that of curcumin-active pharmaceutical ingredients (Cur-API) (about 9.24-fold). The treatment of cell lines with Cur-RH60/F127-MMs exerted a significantly stronger anti-inflammatory effect compared to Cur-API. In addition, Cur-RH60/F127-MMs significantly reduced OVA-induced airway hyperresponsiveness and inflammation in an in vivo experimental asthma model. In conclusion, this study reveals the possibility of formulating a new drug delivery system for curcumin, in particular nanosized micellar aqueous dispersion, which could be considered a perspective platform for the application of curcumin in inflammatory diseases of the airways.

An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption.

Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive1,2. Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.

Association between ambient air pollutants and birthweight of singletons following assisted reproductive technologies.

OBJECTIVE: To investigate the associations between exposure to ambient air pollutants and birthweight following ART treatment. DESIGN: Retrospective cohort study. METHODS: We included 11,599 singletons derived from fresh cycles or frozen-thawed embryo transfer (FET) cycles between Jan 2013 and Dec 2019. Exposure to six air pollutants (SO2, NO2, CO, O3, PM2.5, and PM10) at patients` residences and the clinic site were estimated using the inverse distance weighting interpolation method based on data obtained from monitor sites. The daily mean levels of pollutants were estimated in potential exposure windows (the period from three months before treatment to oocyte retrieval, the period of ovarian stimulation, the period of in vitro culture, the period from embryo transfer to hCG test, the period of entire pregnancy, the 1st, 2nd, and 3rd trimester) were calculated. Generalized additive models adjusted for confounders including maternal age, BMI, and parity were used to evaluate the association between exposures and birthweight. Interaction of exposures and ART-associated factors, such as supraphysiologic estradiol and frozen-thawed, were explored in an XGboost model. MAIN OUTCOME MEASURES: Birthweight and z-score of singletons. RESULTS: In fresh cycles, O3 exposure during the period from three months before treatment to oocyte retrieval and SO2 exposure during in vitro culture at the ART clinic showed a linear association with birthweight (7.24, 95% CI: 1.18-13.31 g per 10 µg/m3 increase in O3; 25.92, 95% CI: 8.26-43.58 g per 10 µg/m3 increase in SO2, respectively). For patients receiving single blastocyst transfer with exposures below the China standard of 20 µg/m3, an increase of 10 µg/m3 in SO2 was associated with a 61.52 (95% CI: 1.13-121.91) g increase in birthweight. In FET cycles, no significant association was found between air pollution and birthweight. XGboost model did not reveal a strong interaction between the exposures and ART-related factors, except for the interactions between O3 exposure and BMI. However, none of the interactions reached a higher rank of importance. CONCLUSIONS: Air pollution exposure during ART treatment may affect the birthweight of the offspring.

Clinicopathological characteristics and prognostic analysis of breast cancer with a hormone receptor status of ER(-)/PR(+).

Background: It is unknown whether ER(-)/PR(+) breast cancer is an independent breast cancer subtype, how it differs from other subtypes, and what its significance is regarding treatment and prognosis. This study compared ER(-)/PR(+) breast cancer with other subtypes to better understand the biological characteristics and prognosis of ER(-)/PR(+) breast cancer, to guide clinical treatment and establish a theoretical foundation. Methods: We retrospectively analyzed data for patients diagnosed with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological characteristics of ER(-)/PR(+) breast cancer, including age, tumor size, lymph node status, HER-2 status, pathological type and histological grade, were compared with other types of breast cancer. A risk scoring system was developed based on independent risk factors influencing prognosis to predict the patient's prognosis, and a nomogram model was created to predict the patient's survival rate. Receiver operating characteristic curve (ROC) and calibration curve was used to evaluate the predictive performance of the nomogram. Results: The rates of T3-4, lymph node positivity, HER-2 positivity, infiltrating non-special pathological type, and G3 were significantly higher in ER(-)/PR(+) than in ER(+)/PR(+) cancer (p <0.001). ER(-)/PR(+) was similar to biological activity of ER(-)/PR(-) type. ER(-)/PR(+)/HER-2(+) patients had a better survival prognosis than ER(-)/PR(+) HER-2(-) patients (p<0.05). The prognosis of ER-/PR+ breast cancer was significantly associated with age, HER-2 status, and T stage. Conclusion: ER(-)/PR(+) breast cancer is more similar to ER(-)/PR(-) breast cancer than other breast cancer subtypes, with an early age of onset, a high proportion of infiltrating non-special types, a high histological grade, and a high HER-2 positivity rate. Whether HER-2 positivity can improve the prognosis of ER(-)/PR(+)breast cancer is worth further discussion. The risk scoring system we developed can effectively distinguish between high-risk and low-risk patients. The nomogram we created had a concordance index of 0.736, and the calibration curve showed good agreement between the predicted and observed outcomes.