Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

A review of dose escalation for FDA-approved products treating solid tumors and hematological malignancies in first-in-human trials.

First-in-human (FIH) dose-escalation trials on oncology should prioritize safety and emphasize efficacy. We reviewed the FIH trials of 67 anti-tumor products approved by the Food and Drug Administration between 2018 and 2023 and found that the "3 + 3" design remains the predominant dose-escalation method (66.2%). The number of patients receiving sub-therapeutic doses is positively correlated with the maximum tolerated dose (MTD) or maximum dose (MD) to starting dose ratio (P = 0.056) and the number of dose levels in trials (P < 0.001). In addition, the proportion of products with a high ratio in antibody drugs is higher than that in small molecules (P < 0.001). The MTD or MD exceeded the label dose by three or more doses in 22.03% of the products. In conclusion, optimizing the starting dose selection method, refining the way of determining doses, and finding alternative indicators to replace toxicity as the endpoints will increase the effectiveness and broaden the beneficiary scope.

Efficacy tumor therapeutic applications of stimuli-responsive block copolymer-based nano-assemblies.

Block copolymers are composed of two or more blocks or segments with different chemical properties via various chemical bonds, which can assemble into nanoparticles with a "core-shell" structure. Due to the benefits of simple functionalization, superior drug-loading capacity, and good biocompatibility, various nano-assemblies based on block copolymers have become widely applied in the treatment of cancers in recent years. These nano-assemblies serve as carriers for anti-tumor bioactive, enhancing drug stability and prolonging their circulation time in vivo, which can reduce the toxic side effects of drugs and improve the therapeutic effect. However, the complex and heterogeneous tumor microenvironment poses challenges to the therapeutic efficacy of these nano-assemblies, having the result in the occurrence of drug resistance and the recurrence of tumors. Consequently, a diverse array of stimuli-responsive nano-assemblies has been devised in order to surmount these obstacles. This article provides a comprehensive overview of the utilization of stimuli-responsive nano-assemblies derived from block copolymers in the context of tumor treatment. The review summarizes block polymers responsive to internal stimuli (like ROS, redox, pH, and enzymes) and external stimuli (like light, and temperature), and discusses current challenges and prospects in this field, aiming to provide novel insights for clinical applications.

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation.

Lipid-coated perfluorocarbon nanodroplets (lp-NDs) hold great promise in bio-medicine as vehicles for drug delivery, molecular imaging and vaccine agents. However, their clinical utility is restricted by limited targeted accumulation, attributed to the innate immune system (IIS), which acts as the initial defense mechanism in humans. This study aimed to optimize lp-ND formulations to minimize non-specific clearance by the IIS. Ginsenosides (Gs), the principal components of Panax ginseng, possessing complement inhibition ability, structural similarity to cholesterol, and comparable fat solubility to phospholipids, were used as promising candidate IIS inhibitors. Two different types of ginsenoside-based lp-NDs (Gs lp-NDs) were created, and their efficacy in reducing IIS recognition was examined. The Gs lp-NDs were observed to inhibit the adsorption of C3 in the protein corona (PC) and the generation of SC5b-9. Adding Gs to lp-NDs reduced complement adsorption and phagocytosis, resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs. These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants, potentially reducing non-specific clearance by the IIS and improving lifespan.

Four new tirucallane-type triterpenoids from Aphanamixis polystachya.

Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.

Blepharoptosis Consultation with Artificial Intelligence: Aesthetic Surgery Advice and Counseling from Chat Generative Pre-Trained Transformer (ChatGPT).

BACKGROUND: Chat generative pre-trained transformer (ChatGPT) is a publicly available extensive artificial intelligence (AI) language model that leverages deep learning to generate text that mimics human conversations. In this study, the performance of ChatGPT was assessed by offering insightful and precise answers to a series of fictional questions and emulating a preliminary consultation on blepharoplasty. METHODS: ChatGPT was posed with questions derived from a blepharoplasty checklist provided by the American Society of Plastic Surgeons. Board-certified plastic surgeons and non-medical staff members evaluated the responses for accuracy, informativeness, and accessibility. RESULTS: Nine questions were used in this study. Regarding informativeness, the average score given by board-certified plastic surgeons was significantly lower than that given by non-medical staff members (2.89 ± 0.72 vs 4.41 ± 0.71; p = 0.042). No statistically significant differences were observed in accuracy (p = 0.56) or accessibility (p = 0.11). CONCLUSIONS: Our results emphasize the effectiveness of ChatGPT in simulating doctor-patient conversations during blepharoplasty. Non-medical individuals found its responses more informative compared with the surgeons. Although limited in terms of specialized guidance, ChatGPT offers foundational surgical information. Further exploration is warranted to elucidate the broader role of AI in esthetic surgical consultations. LEVEL OF EVIDENCE V: Observational study under respected authorities. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Genistein alleviates dextran sulfate sodium-induced colitis in mice through modulation of intestinal microbiota and macrophage polarization.

OBJECTIVES: Ulcerative colitis (UC) is a colonic immune system disorder, manifested with long duration and easy relapse. Genistein has been reported to possess various biological activities. However, it remains unclear whether genistein can ameliorate UC by modulating the homeostasis of the intestinal bacterial community. METHODS: The dextran sodium sulfate (DSS)-induced UC mice were administrated with genistein (20 mg/kg/day) or genistein (40 mg/kg/day) for ten days. The general physical condition of the mice was monitored. After sacrifice, the changes in colon length and colonic pathological morphology were observed. The expression of intestinal barrier proteins, inflammatory cytokines, and macrophage markers in the colon was detected. The composition and metabolic products of the intestinal microbiota were analyzed. RESULTS: Genistein treatment visibly improved body weight change and disease activity index in DSS-induced mice. Genistein treatment ameliorated colonic pathological alterations and promoted the expression of mucin-2 and tight junction proteins. Genistein administration inhibited myeloperoxidase activity and colonic inflammatory cytokines. Furthermore, genistein administration improved the structure of the intestinal microbial community, promoted the production of short-chain fatty acids, and modulated macrophage polarization. CONCLUSIONS: These results revealed that genistein mediated macrophage polarization balance by improving intestinal microbiota and its metabolites, thereby alleviating DSS-induced colitis.

A new loach species of the genus Oreonectes (Teleostei, Cypriniformes, Nemacheilidae) from Guangxi, China.

A new loach species, Oreonectesandongensissp. nov. is described from the Guangxi Zhuang Autonomous Region, China. The new species can be differentiated from other members of the genus by combinations of characters: a developed posterior chamber of the swim bladder, 13-14 branched caudal-fin rays, 8-16 lateral-line pores, body width 12-15% of standard length (SL), interorbital width 42-47% of head length (HL), and caudal peduncle length 11-16% of SL. Bayesian inference phylogenetic analysis based on mitochondrial Cyt b provided strong support for validity of O.andongensissp. nov. (uncorrected p-distance 6.0-7.5%).

Nanoparticle-Mediated Multiple Modulation of Bone Microenvironment To Tackle Osteoarthritis.

Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design of a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded with azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN with a size of 268 nm are stable under physiological conditions, can be specifically taken up by macrophages through the FN-mediated targeting, and can be dissociated in the oxidative inflammatory microenvironment. The G4-TBP NPs-FN loaded with G4-TBP dendrimer having intrinsic anti-inflammatory property and FN having both anti-inflammatory and antioxidative properties display integrated functions of ROS scavenging, hypoxia attenuation, and macrophage M2 polarization, thus protecting macrophages from apoptosis and creating designed bone immune microenvironment for stem cell osteogenic differentiation. These characteristics of the G4-TBP NPs-FN lead to their effective treatment of an OA model in vivo to reduce pathological changes of joints including synovitis inhibition and cartilage matrix degradation and simultaneously promote osteogenic differentiation for bone repair. The developed nanomedicine formulation combining the advantages of both bioactive phosphorus dendrimers and FN to treat OA may be developed for immunomodulatory therapy of different inflammatory diseases.

ProDiv: Prototype-driven consistent pseudo-bag division for whole-slide image classification.

BACKGROUND AND OBJECTIVE: Pathology image classification is one of the most essential auxiliary processes in cancer diagnosis. To overcome the problem of inadequate Whole-Slide Image (WSI) samples with weak labels, pseudo-bag-based multiple instance learning (MIL) methods have attracted wide attention in pathology image classification. In this type of method, the division scheme of pseudo-bags is usually a primary factor affecting classification performance. In order to improve the division of WSI pseudo-bags on existing random/clustering approaches, this paper proposes a new Prototype-driven Division (ProDiv) scheme for the pseudo-bag-based MIL classification framework on pathology images. METHODS: This scheme first designs an attention-based method to generate a bag prototype for each slide. On this basis, it further groups WSI patch instances into a series of instance clusters according to the feature similarities between the prototype and patches. Finally, pseudo-bags are obtained by randomly combining the non-overlapping patch instances of different instance clusters. Moreover, the design scheme of our ProDiv considers practicality, and it could be smoothly assembled with almost all the MIL-based WSI classification methods in recent years. RESULTS: Empirical results show that our ProDiv, when integrated with several existing methods, can deliver classification AUC improvements of up to 7.3% and 10.3%, respectively on two public WSI datasets. CONCLUSIONS: ProDiv could almost always bring obvious performance improvements to compared MIL models on typical metrics, which suggests the effectiveness of our scheme. Experimental visualization also visually interprets the correctness of the proposed ProDiv.

Complete Genome Sequence Analysis of Bacillus subtilis MC4-2 Strain That against Tobacco Black Shank Disease.

The MC4-2 bacterium strain was isolated and purified from the Periplaneta americana intestine as a biocontrol agent with good antagonistic effect against the pathogens of a soil-borne disease called tobacco black shank. The MC4-2 strain was found to have good broad-spectrum inhibition by plate stand-off test. Based on 16S rRNA and gyrB genes, ANI analysis, and other comparative genomics methods, it was determined that the MC4-2 strain was Bacillus subtilis. The complete genome sequence showed that the genome size was 4,076,630 bp, the average GC content was 43.78%, and the total number of CDSs was 4,207. Genomic prediction analysis revealed that a total of 145 genes were annotated by the CAZy, containing mainly GH and CE enzymes that break down carbohydrates such as glucose, chitin, starch, and alginate, and a large number of enzymes involved in glycosylation were present. A total of ten secondary metabolite clusters were predicted, six clusters of which were annotated as surfactin, bacillaene, fengycin, bacillibactin, subtilosin A, and bacilysin. The present investigation found the biological control mechanism of B. subtilis MC4-2, which provides a strong theoretical basis for the best use of this strain in biological control methods and provides a reference for the subsequent development of agents of this bacterium.

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. RESULTS: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. CONCLUSIONS: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

Evaluation of left ventricular flow field changes after stress in patients with nonobstructive coronary artery disease using ultrasonic flow vector imaging.

Purpose: Vector flow mapping and treadmill exercise stress echocardiography were used to evaluate and explore changes in the left ventricular (LV) flow field of patients with nonobstructive coronary artery disease. Methods: Overall, 34 patients with nonobstructive (<50%) left anterior descending coronary artery stenosis (case group) and 36 patients with no coronary artery stenosis (control group) were included. Apical four-, three-, and two-chamber echocardiographic images were collected at rest and during early recovery from treadmill exercise. LV flow field, vortex area, and circulation (cir) changes were recorded in different phases: isovolumetric systole (S1), rapid ejection (S2), slow ejection (S3), isovolumetric diastole (D1), rapid filling (D2), slow filling (D3), and atrial systole (D4). Intra- and inter-group differences were compared before and after exercise loading. Results: The control and case groups demonstrated regular trends of eddy current formation and dissipation at rest and under stress. Compared with the control group, the case group had irregular streamline distributions. Abnormal vortices formed in the S1 and D3 apical segments and D1 left ventricular middle segment in the resting group. Compared with the control group, the resting group had decreased left ventricular S1 vortex areas and increased S3 vortex areas. The post-stress D1 and D3 vortex areas and D1 and D2 cir increased. Compared with at rest, after stress, the control group had decreased S1, S3, D2, and D3 vortex areas; increased S2, D1, D3, and D4 cir; and decreased D2 cir. After stress, the case group had decreased S3 and D2 vortex areas, increased D1 vortex areas, and increased S2, D1, D3, and D4 cir (P all < 0.001). Logistic regression and ROC curve analyses show that increased D1 vortex area after stress is an independent risk factor for stenosis in nonobstructive stenosis of coronary arteries (OR: 1.007, 95% CI: 1.005-1.010, P < 0.05). A D1 vortex area cutoff value of 82.26 had an AUC, sensitivity, and specificity of 0.67, 0.655, and 0.726, respectively. Conclusion: The resting left ventricular flow field changed in patients with nonobstructive left anterior descending coronary artery stenosis. Both groups had more disordered left ventricular blood flow after stress. The increased D1 vortex area after stress is an independent risk factor for mild coronary stenosis and may contribute to the assessment of nonobstructive coronary stenosis. VFM combined with treadmill stress is useful in evaluating left ventricular flow field changes in patients with nonobstructive coronary artery disease, which is valuable in the early evaluation of coronary heart disease.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

Quantum dot fluorescent microsphere-based immunochromatographic strip for detecting PRRSV antibodies.

Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Current vaccine prevention and treatment approaches for PRRS are not adequate, and commercial vaccines do not provide sufficient cross-immune protection. Therefore, establishing a precise, sensitive, simple, and rapid serological diagnostic approach for detecting PRRSV antibodies is crucial. The present study used quantum dot fluorescent microspheres (QDFM) as tracers, covalently linked to the PRRSV N protein, to develop an immunochromatography strip (ICS) for detecting PRRSV antibodies. Monoclonal antibodies against PRRSV nucleocapsid (N) and membrane (M) proteins were both coated on nitrocellulose membranes as control (C) and test (T) lines, respectively. QDFM ICS identified PRRSV antibodies under 10 min with high sensitivity and specificity. The specificity assay revealed no cross-reactivity with the other tested viruses. The sensitivity assay revealed that the minimum detection limit was 1.2 ng/mL when the maximum dilution was 1:2,048, comparable to the sensitivity of enzyme-linked immunosorbent assay (ELISA) kits. Moreover, compared to PRRSV ELISA antibody detection kits, the sensitivity, specificity, and accuracy of QDFM ICS after analyzing 189 clinical samples were 96.7%, 97.9%, and 97.4%, respectively. Notably, the test strips can be stored for up to 6 months at 4 °C and up to 4 months at room temperature (18-25 °C). In conclusion, QDFM ICS offers the advantages of rapid detection time, high specificity and sensitivity, and affordability, indicating its potential for on-site PRRS screening. KEY POINTS: • QDFM ICS is a novel method for on-site and in-lab detection of PRRSV antibodies • Its sensitivity, specificity, and accuracy are on par with commercial ELISA kits • QDFM ICS rapidly identifies PRRSV, aiding the swine industry address the evolving virus.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BACKGROUND: Previous research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental 'inactivity-poor cognition' cycle, is worthy of investigation. METHODS: We used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FINDINGS: Overall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: ß = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: ß = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: ß = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: ß = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (ß = -0.05, 95% CI [-0.08,-0.03], P < 0.01), outdoor activities (ß = -0.02, 95% CI [-0.04, -0.01], P < 0.01) and social activities (ß = -0.02, 95% CI [-0.02, -0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. INTERPRETATION: Our findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

Exquisite visualization of mitophagy and monitoring the increase of lysosomal micro-viscosity in mitophagy with an unusual pH-independent lysosomal rotor.

BACKGROUND: Mitophagy plays indispensable roles in maintaining intracellular homeostasis in most eukaryotic cells by selectively eliminating superfluous components or damaged organelles. Thus, the co-operation of mitochondrial probes and lysosomal probes was presented to directly monitor mitophagy in dual colors. Nowadays, most of the lysosomal probes are composed of groups sensitive to pH, such as morpholine, amine and other weak bases. However, the pH in lysosomes would fluctuate in the process of mitophagy, leading to the optical interference. Thus, it is crucial to develop a pH-insensitive probe to overcome this tough problem to achieve exquisite visualization of mitophagy. RESULTS: In this study, we rationally prepared a pH-independent lysosome probe to reduce the optical interference in mitophagy, and thus the process of mitophagy could be directly monitored in dual color through cooperation between IVDI and MTR, depending on Förster resonance energy transfer mechanism. IVDI shows remarkable fluorescence enhancement toward the increase of viscosity, and the fluorescence barely changes when pH varies. Due to the sensitivity to viscosity, the probe can visualize micro-viscosity alterations in lysosomes without washing procedures, and it showed better imaging properties than LTR. Thanks to the inertia of IVDI to pH, IVDI can exquisitely monitor mitophagy with MTR by FRET mechanism despite the changes of lysosomal pH in mitophagy, and the reduced fluorescence intensity ratio of green and red channels can indicate the occurrence of mitophagy. Based on the properties mentioned above, the real-time increase of micro-viscosity in lysosomes during mitophagy was exquisitely monitored through employing IVDI. SIGNIFICANCE AND NOVELTY: Compared with the lysosomal fluorescent probes sensitive to pH, the pH-inert probe could reduce the influence of pH variation during mitophagy to achieve exquisite visualization of mitophagy in real-time. Besides, the probe could monitor the increase of lysosomal micro-viscosity in mitophagy. So, the probe possesses tremendous potential in the visualization of dynamic changes related to lysosomes in various physiological processes.

Crater-Spectrum Feature Fusion Method for Panax notoginseng Cadmium Detection Using Laser-Induced Breakdown Spectroscopy.

Panax notoginseng (P. notoginseng) is a valuable herbal medicine, as well as a dietary food supplement known for its satisfactory clinical efficacy in alleviating blood stasis, reducing swelling, and relieving pain. However, the ability of P. notoginseng to absorb and accumulate cadmium (Cd) poses a significant environmental pollution risk and potential health hazards to humans. In this study, we employed laser-induced breakdown spectroscopy (LIBS) for the rapid detection of Cd. It is important to note that signal uncertainty can impact the quantification performance of LIBS. Hence, we proposed the crater-spectrum feature fusion method, which comprises ablation crater morphology compensation and characteristic peak ratio correction (CPRC), to explore the feasibility of signal uncertainty reduction. The crater morphology compensation method, namely, adding variables using multiple linear regression (MLR) analysis, decreased the root-mean-square error of the prediction set (RMSEP) from 7.0233 µg/g to 5.4043 µg/g. The prediction results were achieved after CPRC pretreatment using the calibration curve model with an RMSEP of 3.4980 µg/g, a limit of detection of 1.92 µg/g, and a limit of quantification of 6.41 µg/g. The crater-spectrum feature fusion method reached the lowest RMSEP of 2.8556 µg/g, based on a least-squares support vector machine (LSSVM) model. The preliminary results suggest the effectiveness of the crater-spectrum feature fusion method for detecting Cd. Furthermore, this method has the potential to be extended to detect other toxic metals in addition to Cd, which significantly contributes to ensuring the quality and safety of agricultural production.