A branched polymer-based agent for efficient and precise targeting of fibrosis diseases by magnetic resonance imaging.

Herein, we synthesized and characterized gadolinium-based hyperbranched polymers, POADGd and PODGd, through RAFT polymerization as magnetic resonance imaging (MRI) contrast agents for detecting fibrosis. POADGd and PODGd contain biocompatible short-chain OEGMA to prolong blood circulation, and they can be decomposed in response to ROS after MRI examination to prevent potential accumulation. The relaxivities of POADGd and PODGd are 9.81 mM-1 s-1 and 9.58 mM-1 s-1 respectively, which are significantly higher than that of DTPA-Gd, a clinically used agent (3.74 mM-1 s-1). In comparison with PODGd, POADGd can specifically target allysine in fibrosis tissues through its oxyamine groups. Therefore, it displays a sharp spatial resolution and a high signal-to-noise ratio in the liver and lung fibrosis tissue at a field strength of 3.0 T or 7.0 T, and the morphology of these fibrosis tissues is accurately delineated. Our MRI diagnosis results based on POADGd are highly aligned with those from pathological examinations, while MRI diagnosis could avoid invasive biopsy. In addition, POADGd shows excellent biosafety and low toxicity. Therefore, POADGd could be applied to non-invasively and accurately diagnose liver and lung fibrosis diseases.

Design and Synthesis of Sb-doped CuS@C Hollow Nanocubes as Efficient Anode Materials for Sodium-Ion Battery.

CuS have received widespread attention for application as anode materials in sodium-ion batteries due to their potent capabilities and eco-friendly properties. However, it is a challenge to achieve a high rate capability and long cycle stability owing to the heterogeneous transfer of sodium ions during charge-discharge, the interior poor electron conductivity and repeated volumetric expansion of copper sulfide. In this study, Sb-doped CuS hollow nanocubes coated with carbon shells (Sb-CuS@C) was designed and constructed as anode nanomaterials in sodium ion batteries. Thanks to the intrinsic good electron conductivity and chemical stability of carbon shells, Sb-CuS@C possesses a higher overall electron transfer as anode material, avoids agglomeration and structural destruction during the cycling. As a result, the synthesized Sb-CuS@C achieved an excellent reversible capacity of 595 mA h g-1 after 100 cycles at 0.5 A g-1 and a good rate capability of 340 mA h g-1 at a higher 10 A g-1. DFT calculations clarify that the uniformly doped Sb would act as active sodiophilic nucleation sites to help adsorbing Na+ during discharging and leading uniform sodium deposition. This work provides a new insight into the structural and componential modification for common transition-metal sulfides towards application as anode materials in SIB.

Towards sustainable upcycling of side streams of purple bread wheat using dry fractionation: Enhancing bioactive compounds and reducing harmful elements.

Side streams from milling result in significant food wastage. While highly nutritious, their harmful elements raise concerns. To repurpose these side streams safely, this study designed a dry fractionation technique for anthocyanin-rich purple bread wheat. Four fractions - from inner to outer layers: flour, middlings, shorts and bran - alongside whole-wheat flour were obtained and examined by microstructure, antioxidant activity, anthocyanin profiles, and essential and harmful minerals. Across the four investigated cultivars, both anthocyanin content and antioxidant capacity increased from inner to outer layers. In comparison to flour, cyanidin-3-glucoside concentrations in middlings, shorts and bran were 2-5 times, 3-9 times, and 6-19 times, respectively. Concentrations of Cr, Ni, Sr and Ba progressively increased from inner to outer layers, Pb and Se exhibited uniform distribution, while Al was more concentrated in inner layers. These findings indicate that the fractionation technique is effective in deriving valuable ingredients from underexploited side streams, especially bran.

A simple and efficient gene functional analysis method for studying the growth and development of peach seedlings.

Stable genetic transformation of peach [Prunus persica (L.) Batsch] still faces many technical challenges, and existing transient expression methods are limited by tissue type or developmental stage, making it difficult to conduct functional analysis of genes regulating shoot growth. To overcome this dilemma, we developed a three-step method for efficient analysis of gene functions during peach seedling growth and development. This method resulted in transformation frequencies ranging from 48 to 87%, depending on the gene. From transformation of germinating seeds to phenotyping of young saplings took just 1.5 months and can be carried out any time of year. To test the applicability of this method, the function of three tree architecture-related genes, namely PpPDS, PpMAX4, and PpWEEP, and two lateral root-related genes, PpIAA14-1 and -2, were confirmed. Since functional redundancy can challenge gene functional analyses, tests were undertaken with the growth-repressor DELLA, which has three homologous genes, PpDGYLA (DG), PpDELLA1 (D1), and -2 (D2), in peach that are functionally redundant. Silencing using a triple-target vector (TRV2-DG-D1-D2) resulted in transgenic plants taller than those carrying just TRV2-DG or TRV2. Simultaneously silencing the three DELLA genes also attenuated the stature of two dwarf genotypes, 'FHSXT' and 'HSX', which normally accumulate DELLA proteins. Our study provides a method for the functional analysis of genes in peach and can be used for the study of root, stem, and leaf development. We believe this method can be replicated in other woody plants.

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy.

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes (STING) agonist was encapsulated into mB4S. After internalization of mB4S, EPI was acidic-responsively released to induce ICD, which was characterized by an increased level of calreticulin (CRT) exposure and enhanced ATP secretion. Meanwhile, diABZI effectively activated the STING pathway. Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells (DCs) and CD8+ T cells, promoting cytokines secretion, up-regulating M1-like tumor-associated macrophages (TAMs) and down-regulating immunosuppressive myeloid-derived suppressor cells (MDSCs). Therefore, this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+ T cells infiltration, creating an immuno-supportive microenvironment, thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

Gene Editing in the Chagas Disease Vector Rhodnius prolixus by Cas9-Mediated ReMOT Control.

Rhodnius prolixus is currently the model vector of choice for studying Chagas disease transmission, a debilitating disease caused by Trypanosoma cruzi parasites. However, transgenesis and gene editing protocols to advance the field are still lacking. Here, we tested protocols for the maternal delivery of CRISPR-Cas9 (clustered regularly spaced palindromic repeats/Cas-9 associated) elements to developing R. prolixus oocytes and strategies for the identification of insertions and deletions (indels) in target loci of resulting gene-edited generation zero (G0) nymphs. We demonstrate successful gene editing of the eye color markers Rp-scarlet and Rp-white, and the cuticle color marker Rp-yellow, with highest effectiveness obtained using Receptor-Mediated Ovary Transduction of Cargo (ReMOT Control) with the ovary-targeting BtKV ligand. These results provide proof of concepts for generating somatic mutations in R. prolixus and potentially for generating germ line-edited lines in triatomines, laying the foundation for gene editing protocols that could lead to the development of novel control strategies for vectors of Chagas disease.

Bioorthogonal In Situ Polymerization of Dendritic Agents for Hijacking Lysosomes and Enhancing Antigen Presentation in Cancer Cells.

A low-generation lysine dendrimer, SPr-G2, responds to intracellular glutathione to initiate bioorthogonal in situ polymerization, resulting in the formation of large assemblies in mouse breast cancer cells. The intracellular large assemblies of SPr-G2 can interact with lysosomes to induce lysosome expansion and enhance lysosomal membrane permeabilization, leading to major histocompatibility complex class I upregulation on tumor cell surfaces and ultimately tumor cell death. Moreover, the use of the SPr-G2 dendrimer to conjugate the chemotherapeutic drug, camptothecin (CPT), can boost the therapeutic potency of CPT. Excellent antitumor effects in vitro and in vivo are obtained from the combinational treatment of the SPr-G2 dendrimer and CPT. This combinational effect also enhances antitumor immunity through promoting activation of cytotoxic T cells in tumor tissues and maturation of dendritic cells. This study can shed new light on the development of peptide dendritic agents for cancer therapy.

Dendritic Polymer-Based Nanomedicines Remodel the Tumor Stroma: Improve Drug Penetration and Enhance Antitumor Immune Response.

The dense extracellular matrix (ECM) in solid tumors, contributed by cancer-associated fibroblasts (CAFs), hinders penetration of drugs and diminishes their therapeutic outcomes. A sequential treatment strategy of remodeling the ECM via a CAF modifier (dasatinib, DAS) is proposed to promote penetration of an immunogenic cell death (ICD) inducer (epirubicin, Epi) via apoptotic vesicles, ultimately enhancing the treatment efficacy against breast cancer. Dendritic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)-based nanomedicines (poly[OEGMA-Dendron(G2)-Gly-Phe-Leu-Gly-DAS] (P-DAS) and poly[OEGMA-Dendron(G2)-hydrazone-Epi] (P-Epi)) are developed for sequential delivery of DAS and Epi, respectively. P-DAS reprograms CAFs to reduce collagen by downregulating collagen anabolism and energy metabolism, thereby reducing the ECM deposition. The regulated ECM can enhance tumor penetration of P-Epi to strengthen its ICD effect, leading to an amplified antitumor immune response. In breast cancer-bearing mice, this approach alleviates the ECM barrier, resulting in reduced tumor burden and increased cytotoxic T lymphocyte infiltration, and more encouragingly, synergizes effectively with anti-programmed cell death 1 (PD-1) therapy, significantly inhibiting tumor growth and preventing lung metastasis. Furthermore, systemic toxicity is barely detectable after sequential treatment with P-DAS and P-Epi. This approach opens a new avenue for treating desmoplastic tumors by metabolically targeting CAFs to overcome the ECM barrier.

Elevated liver enzymes in the first trimester are associated with gestational diabetes mellitus: A prospective cohort study.

AIMS: Previous studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors. METHODS: This prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid-pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back-propagation artificial neural network was performed to rank independently risk factors of GDM. RESULTS: Women diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all p < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (ORs) ranging from 2.76 to 8.11 (all p < 0.05). Moreover, the ORs of GDM increased linearly with liver enzymes level (all P for overall association <0.001). Furthermore, Back-propagation artificial neural network identified γ-gamma-glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%). CONCLUSIONS: Single or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.

Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier.

DNA double-strand breaks (DSBs) are repaired by a hierarchically regulated network of pathways. Factors influencing the choice of particular repair pathways, however remain poorly characterized. Here we develop an Integrated Classification Pipeline (ICP) to decompose and categorize CRISPR/Cas9 generated mutations on genomic target sites in complex multicellular insects. The ICP outputs graphic rank ordered classifications of mutant alleles to visualize discriminating DSB repair fingerprints generated from different target sites and alternative inheritance patterns of CRISPR components. We uncover highly reproducible lineage-specific mutation fingerprints in individual organisms and a developmental progression wherein Microhomology-Mediated End-Joining (MMEJ) or Insertion events predominate during early rapid mitotic cell cycles, switching to distinct subsets of Non-Homologous End-Joining (NHEJ) alleles, and then to Homology-Directed Repair (HDR)-based gene conversion. These repair signatures enable marker-free tracking of specific mutations in dynamic populations, including NHEJ and HDR events within the same samples, for in-depth analysis of diverse gene editing events.

A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes.

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of - 0.11 (95% CI - 0.15, - 0.07, Z = 5.45; P < 0.00001). Subgroup analyses performed on adult vs pediatric patients showed a similar association of antibiotic on cognition in both subgroups. Antibiotic treatment was not associated with worse cognition on subjects with existing cognitive impairment. On the other hand, antibiotic treatment on subjects with no prior cognitive impairment was associated with worse cognitive performance later in life. This calls for future well-designed and well-powered studies to investigate the impact of antibiotics on cognitive performance.

Mediating Effect of Insulin-Like Growth Factor-I Underlying the Link Between Vitamin D and Gestational Diabetes Mellitus.

Vitamin D was well-known to be associated with gestational diabetes mellitus (GDM). Insulin-like growth factor-I (IGF-I) has been linked to vitamin D and GDM, respectively. We hypothesize that changes in IGF-I metabolism induced by 25(OH)D3 might contribute to GDM. Therefore, we investigated the independent and combined relationships of serum 25(OH)D3 and IGF-I concentrations with GDM risk, and the mediation effect of IGF-I on 25(OH)D3. A total of 278 pregnant women (including 125 cases and 153 controls) were recruited in our current study. Maternal serum 25(OH)D3 and IGF-I were measured in the second trimester. Logistic regression models were used to estimate the associations of 25(OH)D3 and IGF-I concentrations with the risk of GDM. Mediation analyses were used to explore the mediation effect of IGF-I on the association between 25(OH)D3 and the risk of GDM. After adjusted for the confounded factors, both the third and fourth quartile of 25(OH)D3 decreased the risk of GDM (OR = 0.226; 95% CI, 0.103-0.494; OR = 0.109; 95% CI, 0.045-0.265, respectively) compared to the first quartile of 25(OH)D3. However, the third and fourth quartile of serum IGF-I (OR = 5.174; 95% CI, 2.287-11.705; OR = 12.784; 95% CI, 5.292-30.879, respectively) increased the risk of GDM compared to the first quartile of serum IGF-I. Mediation analyses suggested that 19.62% of the associations between 25(OH)D3 and GDM might be mediated by IGF-I. The lower concentration of serum 25(OH)D3 or higher IGF-I in the second trimester was associated with an increased risk of GDM. The serum IGF-I level might be a potential mediator between 25(OH)D3 and GDM.

A rapid and efficient Agrobacterium-mediated transient transformation system in grape berries.

Transient transformation is extremely useful for rapid in vivo assessment of gene function, especially for fruit-related genes. Grape berry, while an important fruit crop, is recalcitrant to transient transformation, due to the high turgor pressure in its mesocarp cells that limits the ability of Agrobacterium to penetrate into the tissue. It is urgent to establish a simple transient transformation system for rapid analysis of gene function. In this study, different injection methods, grape genotypes, and developmental stages were tested in order to develop a rapid and efficient Agrobacterium-mediated transient transformation methodology for grape berries. Two injection methods, namely punch injection and direct injection, were evaluated using the ß-glucuronidase (GUS) gene and by x-gluc tissue staining and 4-methylumbelliferyl-ß-D-glucuronide fluorescence analysis. The results indicated that there were no significant differences on transformation effects between the two methods, but the latter was more suitable because of its simplicity and convenience. Six grape cultivars ('Hanxiangmi', 'Moldova', 'Zijixin', 'Jumeigui', 'Shine-Muscat', and 'A17') were tested for transient transformation. 'Hanxiangmi', 'Moldova', and 'Zijixin' grape berries were not suitable for agroinfiltration due to frequently fruit cracking, browning, and formation of scar skin. The fruit integrity rates of 'Jumeigui', 'Shine-Muscat', and 'A17' berries were all above 80%, and GUS activity was detected in the berries of the three cultivars 3-14 days after injection with the Agrobacterium culture, while higher GUS activities were observed in the 'Jumeigui' berries. The levels of GUS activity in injected berries at 7-8 weeks after full blooming (WAFB) were more than twice at 6 WAFB. In subsequent assays, the over-expression of MYB transcription factor VvMYB44 via transient transformation accelerated the anthocyanin accumulation and fruit coloring through raising the expression levels of VvLAR1, VvUFGT, VvLDOX, VvANS, and VvDFR, which verified the effectiveness of this transformation system. These experiments finally identified the reliable grape cultivars and suitable operational approach for transient transformation and further indicated that this Agrobacterium-mediated transient transformation system was efficient and suitable for the elucidation of gene function in grape berries.

Chitosan-based hydrogel dressings for diabetic wound healing via promoting M2 macrophage-polarization.

A long-term inflammatory phase of diabetic wounds is the primary cause to prevent their effective healing. Bacterial infection, excess reactive oxygen species (ROS), especially failure of M2-phenotype macrophage polarization can hinder the transition of diabetic wounds from an inflammation phase to a proliferation one. Herein, a chitosan-based hydrogel dressing with the ability of regulating M2 macrophage polarization was reported. The PAAc/CFCS-Vanillin hydrogel dressing was synthesized by one step thermal polymerization of catechol-functionalized chitosan (CFCS), acrylic acid, catechol functional methacryloyl chitosan­silver nanoparticles (CFMC-Ag NPs) and bioactive vanillin. The PAAc/CFCS-Vanillin hydrogel possessed sufficient mechanical strength and excellent adhesion properties, which helped rapidly block bleeding of wounds. Thanks to CFCS, CFMC-Ag NPs and vanillin in the hydrogel, it displayed excellent antibacterial infection in the wounds. Vanillin helped scavenge excess ROS and regulate the levels of inflammatory factors to facilitate the polarization of macrophages into the M2 phenotype. A full-thickness skin defect diabetic wound model showed that the wounds treated by the PAAc/CFCS-Vanillin hydrogel exhibited the smallest wound area, and superior granulation tissue regeneration, remarkable collagen deposition, and angiogenesis were observed in the wound tissue. Therefore, the PAAc/CFCS-Vanillin hydrogel could hold promising potential as a dressing for the treatment of diabetic chronic wounds.

Enzyme-Responsive Branched Glycopolymer-Based Nanoassembly for Co-Delivery of Paclitaxel and Akt Inhibitor toward Synergistic Therapy of Gastric Cancer.

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.

Co-assembly of polymeric conjugates sensitizes neoadjuvant chemotherapy of triple-negative breast cancer with reduced systemic toxicity.

Rational design of polymeric conjugates could greatly potentiate the combination therapy of solid tumors. In this study, we designed and prepared two polymeric conjugates (HT-DTX and PEG-YC-1), whereas the drugs were attached to the PEG via a linker sensitive to cathepsin B, over-expressed in TNBC. Stable nanostructures were formed by these two polymer prodrug conjugates co-assembly (PPCC). The stimuli-responsiveness of PPCC was confirmed, and the size shrinkage under tumor microenvironment would facilitate the penetration of PPCC into tumor tissue. In vitro experiments revealed the molecular mechanism for the synergistic effect of the combination of DTX and YC-1. Moreover, the systemic side effects were significantly diminished since the biodistribution of PPCC was improved after i.v. administration in vivo. In this context, the co-assembled nano-structural approach could be employed for delivering therapeutic drugs with different mechanisms of action to exert a synergistic anti-tumor effect against solid tumors, including triple-negative breast cancer. STATEMENT OF SIGNIFICANCE.

Stimuli-activatable nanomedicine meets cancer theranostics.

Stimuli-activatable strategies prevail in the design of nanomedicine for cancer theranostics. Upon exposure to endogenous/exogenous stimuli, the stimuli-activatable nanomedicine could be self-assembled, disassembled, or functionally activated to improve its biosafety and diagnostic/therapeutic potency. A myriad of tumor-specific features, including a low pH, a high redox level, and overexpressed enzymes, along with exogenous physical stimulation sources (light, ultrasound, magnet, and radiation) have been considered for the design of stimuli-activatable nano-medicinal products. Recently, novel stimuli sources have been explored and elegant designs emerged for stimuli-activatable nanomedicine. In addition, multi-functional theranostic nanomedicine has been employed for imaging-guided or image-assisted antitumor therapy. In this review, we rationalize the development of theranostic nanomedicine for clinical pressing needs. Stimuli-activatable self-assembly, disassembly or functional activation approaches for developing theranostic nanomedicine to realize a better diagnostic/therapeutic efficacy are elaborated and state-of-the-art advances in their structural designs are detailed. A reflection, clinical status, and future perspectives in the stimuli-activatable nanomedicine are provided.

Research on a Multimodel Fusion Diagnosis Method for Evaporation Ducts in the East China Sea.

Evaporation ducts are abnormal states of the atmosphere in the air-sea boundary layer that directly affect the propagation trajectory of electromagnetic (EM) waves. Therefore, an accurate diagnosis of the evaporation duct height (EDH) is important for studying the propagation trajectory of EM waves in evaporation ducts. Most evaporation duct models (EDMs) based on the Monin-Obukhov similarity theory are empirical methods. Different EDMs have different levels of environmental adaptability. Evaporation duct diagnosis methods based on machine learning methods only consider the mathematical relationship between data and do not explore the physical mechanism of evaporation ducts. To solve the above problems, this study observed the meteorological and hydrological parameters of the five layers of the low-altitude atmosphere in the East China Sea on board the research vessel Xiangyanghong 18 in April 2021 and obtained the atmospheric refractivity profile. An evaporation duct multimodel fusion diagnosis method (MMF) based on a library for support vector machines (LIBSVM) is proposed. First, based on the observed meteorological and hydrological data, the differences between the EDH diagnosis results of different EDMs and MMF were analyzed. When ASTD ≥ 0, the average errors of the diagnostic results of BYC, NPS, NWA, NRL, LKB, and MMF are 2.57 m, 2.92 m, 2.67 m, 3.27 m, 2.57 m, and 0.24 m, respectively. When ASTD < 0, the average errors are 2.95 m, 2.94 m, 2.98 m, 2.99 m, 2.97 m, and 0.41 m, respectively. Then, the EM wave path loss accuracy analysis was performed on the EDH diagnosis results of the NPS model and the MMF. When ASTD ≥ 0, the average path loss errors of the NPS model and MMF are 5.44 dB and 2.74 dB, respectively. When ASTD < 0, the average errors are 5.21 dB and 3.46 dB, respectively. The results show that the MMF is suitable for EDH diagnosis, and the diagnosis accuracy is higher than other models.

Dendritic polymer-functionalized nanomedicine potentiates immunotherapy via lethal energy crisis-induced PD-L1 degradation.

The advent of immune checkpoint inhibitors ushers in a new era of anti-tumor immunity. However, current clinical anti-PD-L1 antibodies only interdict PD-L1 on the membrane, which cannot diminish the complex cancer-promoting effects of intracellular PD-L1. Therefore, directly reducing the PD-L1 abundance of cancer cells might be a potential PD-L1 inhibitory strategy to circumvent the issues of current anti-PD-L1 antibodies. Herein, we develop a dendritic polymer-functionalized nanomedicine with a potent cellular energy depletion effect on colon cancer cells. Treatment with the nanomedicine significantly promotes phosphorylation of AMPK, which in turn leads to PD-L1 degradation and eventual T cell activation. Meanwhile, the nanomedicine can potently induce immunogenic cell death (ICD) to enhance the anti-cancer immunity. Moreover, the combination of the nanomedicine with PD-1 blockade further enhances the activity of cytotoxic T lymphocytes, and dramatically inhibits tumor growth in vivo without distinct side effects. Overall, this study provides a promising nanoplatform to induce lethal energy crisis and ICD, and suppress PD-L1 expression, thus potentiating cancer immunotherapy.

Effects of behaviors and surrounding environment on myopia before and during the COVID-19 pandemic: a longitudinal analysis of children and adolescents in China.

Aim: To investigate the relationship between related factors and visual acuity of Chinese school students before and during the COVID-19 pandemic. Subject and methods: Chinese students from primary and secondary schools were included from the Chinese National Surveys on Students' Constitution and Health CNSSCH (2019). A total of 1496 participants completed follow-ups in June and December 2020, respectively. Generalized estimating equations were used to test the differences in visual environment. Logistic regression models were utilized to examine the roles of behaviors and surrounding environment changes associated with myopia before and during the pandemic. Results: The prevalence of myopia was 47.7%, 55.6%, and 57.2% in baseline and two follow-ups, respectively. Significant differences existed for gender, learning level, and region (all P < 0.05). The proportion of new myopia and myopia torsion was the highest in the primary schools. Multivariate logistic regression analysis found that screen time ≥ 4h/d (OR = 2.717), poor eye habits (OR = 1.477), insufficient lighting for studying at night (OR = 1.779), desk or roof lamps only (OR = 1.388), and poor sleep quality (OR = 4.512) were the risk factors for myopia (all P < 0.05), and eye exercises (OR = 0.417), milk intake (OR = 0.758), and eggs intake (OR = 0.735) were the protective factors for myopia (all P < 0.05). Conclusion: Prevalence of myopia increased among Chinese students before and during the COVID-19. It is necessary to pay more attention to the pupils' visual acuity, especially in primary school students, in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01900-w.