Gendered citation patterns among the scientific elite.

Diversity in science is necessary to improve innovation and increase the capacity of the scientific workforce. Despite decades-long efforts to increase gender diversity, however, women remain a small minority in many fields, especially in senior positions. The dearth of elite women scientists, in turn, leaves fewer women to serve as mentors and role models for young women scientists. To shed light on gender disparities in science, we study prominent scholars who were elected to the National Academy of Sciences. We construct author citation networks that capture the structure of recognition among scholars' peers. We identify gender disparities in the patterns of peer citations and show that these differences are strong enough to accurately predict the scholar's gender. In contrast, we do not observe disparities due to prestige, with few significant differences in the structure of citations of scholars affiliated with high-ranked and low-ranked institutions. These results provide further evidence that a scholar's gender plays a role in the mechanisms of success in science.

Colon Targeting pH-Responsive Coacervate Microdroplets for Treatment of Ulcerative Colitis.

Ulcerative colitis (UC), an immune-mediated chronic inflammatory disease, drastically impacts patients' quality of life and increases their risk of colorectal cancer worldwide. However, effective oral targeted delivery and retention of drugs in colonic lesions are still great challenges in the treatment of UC. Coacervate microdroplets, formed by liquid-liquid phase separation, are recently explored in drug delivery as the simplicity in fabrication, spontaneous enrichment on small molecules and biological macromolecules, and high drug loading capacity. Herein, in this study, a biocompatible diethylaminoethyl-dextran hydrochloride/sodium polyphenylene sulfonate coacervates, coated with eudragit S100 to improve the stability and colon targeting ability, named EU-Coac, is developed. Emodin, an active ingredient in traditional Chinese herbs proven to alleviate UC symptoms, is loaded in EU-Coac (EMO@EU-Coac) showing good stability in gastric acid and pepsin and pH-responsive release behavior. After oral administration, EMO@EU-Coac can effectively target and retain in the colon, displaying good therapeutic effects on UC treatment through attenuating inflammation and oxidative stress response, repairing colonic epithelia, as well as regulating intestinal flora balance. In short, this study provides a novel and facile coacervate microdroplet delivery system for UC treatment.

Molecular mapping and candidate gene identification of two major quantitative trait loci associated with silique length in oilseed rape (Brassica napus L.).

Rapeseed is a significant global source of plant oil. Silique size, particularly silique length (SL), impacts rapeseed yield. SL is a typical quantitative trait controlled by multiple genes. In our previous study, we constructed a DH population of 178 families known as the 158A-SGDH population. In this study, through SL QTL mapping, we identified twenty-six QTL for SL across five replicates in two environments. A QTL meta-analysis revealed eight consensus QTL, including two major QTL: cqSL.A02-1 (11.32-16.44% of PVE for SL), and cqSL.C06-1 (10.90-11.95% of PVE for SL). Based on biparental resequencing data and microcollinearity analysis of target regions in Brassica napus and Arabidopsis, we identified 11 candidate genes at cqSL.A02-1 and 6 candidate genes at cqSL.C06-1, which are potentially associated with silique development. Furthermore, transcriptome analysis of silique valves from both parents on the 14th, 21st, and 28th days after pollination (DAP) combined with gene function annotation revealed three significantly differentially expressed genes at cqSL.A02-1, BnaA02G0058500ZS, BnaA02G0060100ZS, and BnaA02G0060900ZS. Only the gene BnaC06G0283800ZS showed significant differences in parental transcription at cqSL.C06-1. Two tightly linked insertion-deletion markers for the cqSL.A02-1 and cqSL.C06-1 loci were developed. Using these two QTL, we generated four combinations: A02SGDH284C06158A, A02SGDH284C06SGDH284, A02158AC06158A, and A02158AC06SGDH284. Subsequent analysis identified an ideal QTL combination, A02158AC06SGDH284, which exhibited the longest SL of this type, reaching 6.06 ± 0.10 cm, significantly surpassing the other three combinations. The results will provide the basis for the cloning of SL-related genes of rapeseed, along with the development of functional markers of target genes and the breeding of rapeseed varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01464-x.

Injectable Liquid Crystal Formation System for Reshaping Tumor Immunosuppressive Microenvironment to Boost Antitumor Immunity: Postoperative Chemoimmunotherapy.

Exploring optimal strategies to improve patient outcome postoperatively is still under challenge. Cancer immunotherapy has great potential to prevent the postoperative tumor recurrence and metastasis, which could be further strengthened by re-education of tumor microenvironment (TME). Herein, a local and sustained drug delivery system of liquid crystal formation system (LCFS) co-loaded with doxorubicin (DOX) and resiquimod (R848) (D/R@LCFS) is reported to confer effective chemoimmunotherapy with reduced systematic toxicity. After local administration, D/R@LCFS turns tumor into in situ vaccine via DOX-triggered immunogenic cell death effect accompanied with immunostimulatory effect of R848. Meanwhile, combination treatment of D/R@LCFS facilitates the recruitment of effector CD8+ T cells and the polarization of myeloid-derived suppressor cells and immunosuppressive type 2-polarized macrophages to tumoricidal antigen-presenting cells, favoring antigen-specific T cell immune response and inducing more immunogenic phenotypes in tumors. The generated in situ vaccine as well as reshaped TME by D/R@LCFS elicited systematic immune response and long term immune-memory effect in combination with immune checkpoint blockade to significantly prevent postoperative B16F10 or 4T1 tumor recurrence and metastasis. Therefore, this combination strategy of spatiotemporal TME modulation is expected to provide a clinical available option for effective postoperative chemoimmunotherapy.

Biofunctional coacervate-based artificial protocells with membrane-like and cytoplasm-like structures for the treatment of persistent hyperuricemia.

Coacervate droplets formed by liquid-liquid phase separation have attracted considerable attention due to their ability to enrich biomacromolecules while preserving their bioactivities. However, there are challenges to develop coacervate droplets as delivery vesicles for therapeutics resulting from the lack of physiological stability and inherent lack of membranes in coacervate droplets. Herein, polylysine-polynucleotide complex coacervate droplets with favorable physiological stability are formulated to efficiently and facilely concentrate small molecules, biomacromolecules and nanoparticles without organic solvents. To improve the biocompatibility, the PEGylated phospholipid membrane is further coated on the surface of the coacervate droplets to prepare coacervate-based artificial protocells (ArtPC) with membrane-like and cytoplasm-like structures. The ArtPC can confine the cyclic catalytic system of uricase and catalase inside to degrade uric acid and deplete the toxicity of H2O2. This biofunctional ArtPC effectively reduces blood uric acid levels and prevents renal injuries in mice with persistent hyperuricemia. The ArtPC-based therapy can bridge the disciplines of synthetic biology, pharmaceutics and therapeutics.

Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma.

AIM: To assess the performance of macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and 10-2 visual field (VF) parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma. METHODS: Totally 127 eyes from 89 participants (36 eyes of 19 healthy participants, 45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients) were included. The relationships between the optical coherence tomography (OCT)-derived parameters and VF sensitivity were determined. Patients with early glaucoma were divided into eyes with or without central 10° of the VF damages (CVFDs), and the diagnostic performances of OCT-derived parameters were assessed. RESULTS: In early glaucoma, the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation (PSD; with average mGCIPLT: ß=-0.046, 95%CI, -0.067 to -0.024, P<0.001). In advanced glaucoma, the mGCIPLT was related to the 24-2 VF mean deviation (MD; with average mGCIPLT: ß=0.397, 95%CI, 0.199 to 0.595, P<0.001), 10-2 VF MD (with average mGCIPLT: ß=0.762, 95%CI, 0.485 to 1.038, P<0.001) and 24-2 VF PSD (with average mGCIPLT: ß=0.244, 95%CI, 0.124 to 0.364, P<0.001). Except for the minimum and superotemporal mGCIPLT, the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs. The area under the curve (AUC) of the average mGCIPLT (AUC=0.949, 95%CI, 0.868 to 0.982) was greater than that of the average circumpapillary retinal nerve fiber layer thickness (cpRNFLT; AUC=0.827, 95%CI, 0.674 to 0.918) and rim area (AUC=0.799, 95%CI, 0.610 to 0.907) in early glaucomatous eyes with CVFDs versus normal eyes. CONCLUSION: The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF, cpRNFLT and ONH parameters, especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

Engineered Biomimetic Nanovesicles Based on Neutrophils for Hierarchical Targeting Therapy of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a clinically severe respiratory disease that causes severe medical and economic burden. To improve therapeutic efficacy, effectively targeting delivery to the inflamed lungs and inflamed cells remains an ongoing challenge. Herein, we designed engineered biomimetic nanovesicles (DHA@ANeu-DDAB) by fusion of lung-targeting functional lipid, neutrophil membrane containing activated ß2 integrins, and the therapeutic lipid, docosahexaenoic acid (DHA). By the advantage of lung targeting lipid and ß2 integrin targeting adhesion, DHA@ANeu-DDAB can first target lung tissue and further target inflammatory vascular endothelial cells, to achieve "tissue first, cell second" hierarchical delivery. In addition, the ß2 integrins in DHA@ANeu-DDAB could bind to the intercellular cell adhesion molecule-1/2 (ICAM-1/2) ligand on the endothelium in the inflamed blood vessels, thus inhibiting neutrophils' infiltration in the blood circulation. DHA administration to inflamed lungs could effectively regulate macrophage phenotype and promote its anti-inflammatory activity via enhanced biosynthesis of specialized pro-resolving mediators. In the lipopolysaccharide-induced ARDS mouse model, DHA@ANeu-DDAB afforded a comprehensive and efficient inhibition of lung inflammation and promoted acute lung damage repair. Through mimicking physiological processes, these engineered biomimetic vesicles as a delivery system possess good potential in targeting therapy for ARDS.

Magnetic resonance imaging assessment of the lateral geniculate nucleus volume and height in patients with glaucoma: a Meta-analysis.

AIM: To evaluate the lateral geniculate nucleus (LGN) volume and height using magnetic resonance imaging (MRI) in glaucoma patients. METHODS: Literatures retrieval was carried out through PubMed, Web of Science, Embase, and Cochrane Library. Studies that compared the volume and height of LGN in glaucoma patients with that in control subjects were included. The volume and height of LGN were extracted from the included studies. The Review Manager 5.4.1 software was used for the Meta-analysis. RESULTS: This Meta-analysis included 10 cross-sectional studies, including the eyes of 223 glaucoma patients and 185 healthy controls. Compared with the control subjects, the volume and height of LGN in glaucoma patients measured by MRI were significantly reduced {-29.13 mm3, 95% [confidence interval (CI): -44.82 to -13.43, P=0.0003; -0.61 mm, 95%CI: -0.78 to -0.44, P<0.00001, respectively]}. Subgroup analysis demonstrated that the differences of LGN volume and height between glaucoma patients and control subjects in the older group were smaller than that in the younger group, and LGN volume decreased with the increase of glaucoma severity. CONCLUSION: The results demonstrate that the volume and height of LGN are decreased in glaucoma patients, and LGN volume can be considered a parameter of glaucoma severity.

Boosting B Cell and Macrophage-Mediated Humoral Immunity with Fusion Nanovesicles for Triple-Negative Breast Cancer Combined Therapy.

Cell-derived nanovesicles are widely utilized as therapeutic agents for cancer therapy. Current research mostly focuses on their ability to activate antitumor cellular immunity. However, whether they can activate and participate in antitumor humoral immunity is rarely studied. Here, doxorubicin-loaded hybrid cell nanovesicles (DNVs) are designed for boosting antitumor humoral and cellular immunity. The hybrid cell nanovesicles are generated through fusion of nanovesicles derived from M1-type macrophages and 4T1 tumor cells. It is found that DNVs can accumulate at tumor tissues and draining lymph nodes effectively, which results in the activation of antitumor immune response and significant inhibition of tumor progression. During this process, dendritic cells are effectively activated, subsequently inducing cytotoxicity T lymphocytes-mediated cellular immunity. Furthermore, DNVs elicit the antitumor humoral immunity through boosting T follicular helper cells and germinal center B cells. By analyzing the mechanism behind humoral immunity activation, it is found that M1-type macrophages repolarized by DNVs play an important role. In general, besides antitumor cellular immunity, the proposed hybrid nanovesicles provide a promising strategy for enhancing antitumor humoral immunity by macrophages repolarization and germinal center B cells activation.

Transition of carbon-nitrogen coupling under different anthropogenic disturbances in subtropical small mountainous rivers.

The commonly observed inverse relationship between dissolved organic carbon (DOC) and nitrate (NO3-) concentrations in aquatic systems can be explained by stoichiometric and thermodynamic principles regulating microbial assimilation and dissimilation processes. However, the interactive effects of human activities and dissolved oxygen (DO) on the DOC and DIN (dissolved inorganic nitrogen, mainly composed of NO3--N and NH4+-N) relations are not well identified, particularly in subtropical small mountainous rivers (SMRs). Here, we investigated the exports and relations of DOC-DIN in 42 Taiwan SMRs under different anthropogenic disturbances. Results showed that the island-wide mean concentrations of the three solutes in streams are generally low, yet the abundant rainfall and persistent supply contrarily lead to disproportional high DOC and DIN yields. The inverse DOC-NO3--N relation does not appear under well­oxygenated conditions, regardless of low or high human disturbance. However, a significant inverse relationship between DOC-NO3--N would emerge in highly-disturbed watersheds under low-oxygenated conditions (mean annual DO <6.5 mg L-1), where excess N accumulates as NH4+-N rather than NO3--N. The controlling mechanism of DOC-DIN relations would shift from energetic constraints to redox constraints in low-oxygenated conditions. Although riverine concentrations of DOC, NO3--N, and NH4+-N could be elevated by human activities, the transition of DOC-DIN relation pattern is directly linked to DO availability. Understanding the mechanism that drives CN coupling is critical for assessing the ecosystem function in the delivery and retention of DOC and DIN in aquatic ecosystems.

The association of bisphenol A and paraben exposure with sensorineural hearing loss in children.

Bisphenol A (BPA) and parabens (PBs) are chemicals that are extensively used in personal care products (PCPs). In early childhood development, hearing is critical to speech and language development, communication, and learning. In vitro and in vivo, BPA/PBs exhibited neurotoxicity through elevated levels of oxidative stress. BPA also has the potential to be an ototoxicant. Therefore, this study aimed to determine the association of exposure to BPA/PBs with sensorineural hearing loss in children. A cross-sectional study based on hearing tests was conducted. This study enrolled 320 children aged 6-12 years from elementary school. Urinary BPA and PB concentrations were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Logistic regression models were employed to determine the association of BPA/PB exposure with sensorineural hearing loss. Children with sensorineural hearing loss had higher BPA concentrations than normal-hearing children (0.22 ng/ml vs. 0.10 ng/ml, p = 0.05). After adjustment for covariates, the risk of hearing loss at middle frequencies reached 1.83-fold (95% CI: 1.12-2.99) when BPA concentrations increased by 1 log10. The risk of slight hearing loss reached 2.24-fold (95% CI: 1.05-4.78) when children had a tenfold increase in ethyl paraben (EP) concentration. This study clarifies the role of exposure to BPA/PBs in hearing loss in children. Future research needs to be expanded to include cohort designs and nationwide studies to identify causality.

Hybrid Biomimetic Nanovesicles to Drive High Lung Biodistribution and Prevent Cytokine Storm for ARDS Treatment.

Acute respiratory distress syndrome (ARDS) has been a life threat for patients in ICUs. Vast efforts have been devoted, while no medication has proved viable, which may be ascribed to inadequate drug delivery to damaged tissues and insufficient control of lung inflammation. Given the anti-inflammatory role of M2-type macrophages, M2 macrophage-derived nanovesicles and lung-targeting liposomes are cofused to fabricate hybrid liposomes-nanovesicles (LNVs). Benefiting from the incorporated lung-homing moiety, LNVs demonstrate high pulmonary accumulation with a lung/liver ratio of 14.9, which is approximately 53.3-fold of free nanovesicles. Thus, M2 macrophage-derived nanovesicles can be delivered to lung tissues for executing immunoregulatory functions. LNVs display phagocytosis by the infiltrated neutrophils and macrophages, exhibiting sustained release of preloaded IKK-2 inhibitor (TPCA-1). The integrated nanosystems demonstrate multidimensional suppression of the overwhelming inflammation, such as decreasing infiltration of inflammatory cells, achieving restraint on cytokine storms and alleviating oxidative stress. Therefore, the improved therapeutic outcome in ARDS mice is obtained. Altogether, the hybrid nanoplatform provides a versatile drug delivery paradigm for integrating biological nanovesicles and therapeutic molecules by cofusion of nanovesicles with liposomes, improving lung biodistribution and accomplishing a boosted anti-inflammatory response for ARDS therapy.

Immunogenic Hybrid Nanovesicles of Liposomes and Tumor-Derived Nanovesicles for Cancer Immunochemotherapy.

Exploring a rational delivery system of integrating chemotherapy with immunotherapy to broaden benefits of cancer immunochemotherapy is still under challenge. Herein, we developed doxorubicin (DOX)-loaded biomimetic hybrid nanovesicles (DOX@LINV) via fusing artificial liposomes (LIPs) with tumor-derived nanovesicles (TNVs) for combinational immunochemotherapy. DOX@LINV with a homologous targeting ability could deliver DOX to tumor tissue and elicit an effective immunogenic cell death response to improve the immunogenicity of a tumor. Meanwhile, the preserved tumor antigens and endogenous danger signals in DOX@LINV activated dendritic cells and induced a subsequent antigen-specific T cell immune response. DOX@LINV displayed a specific antitumor effect on murine melanoma, Lewis lung cancer, and 4T1 breast cancer based on the infiltration of effector immune cells and improvement of the immunosuppressive tumor microenvironment. Furthermore, the combination of DOX@LINV with immune checkpoint inhibitor amplified antitumor efficacy with 33.3% of the mice being tumor-free. Therefore, the hybrid LINV is a promising drug delivery platform with a boosted antitumor immune response for effective immunochemotherapy.

Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade.

Improving tumor immunogenicity is critical for increasing the responsiveness of triple-negative breast cancer (TNBC) to anti-PD-(L)1 treatment. Here, we verified that chidamide (CHI), an epigenetic modulator, could elicit immunogenic cell death within TNBC to enhance cancer immunogenicity and elicit an antitumor immune response. Additionally, CHI increased the expression level of PD-L1, MHC I, and MHC II on cancer cells, which contributed to T-cell recognition and PD-1/PD-L1 blockade therapy response. The synergistic antitumor efficacy of CHI and PD-L1 blockade therapy was further explored through liposomes co-delivering CHI and BMS-202 (a small-molecule PD-L1 inhibitor). The liposomes possessed good biocompatibility, security, and controllable drug release and endowed therapeutics drugs with favorable tumor accumulation. Furthermore, the drug-loaded liposomes could obviously boost the antitumor immunity of TNBC through CHI-enhanced tumor immunogenicity and BMS-202-mediated PD-L1 blockade, thereby effectively inhibiting the growth of primary and metastatic tumors with an inhibitory rate of metastasis of up to 96%. In summary, this work provided a referable and optional approach for clinical antitumor therapy based on the combination of an epigenetic modulator and PD-1/PD-L1 blockade therapy.

Co-Delivery of Paclitaxel and Interleukin-12 Regulating Tumor Microenvironment for Cancer Immunochemotherapy.

In the treatment of malignant tumors, the combination of chemotherapy that can directly kill tumor cells and immunotherapy that can activate the body's immune system and regulate tumor microenvironments is becoming one of the most promising cancer treatments. However, to co-deliver agents with different physicochemical properties for immunochemotherapy is still facing a challenge. Here, nanoparticles are developed for the co-delivery of the hydrophobic chemotherapeutic drug paclitaxel (PTX) and biomacromolecule interleukin-12 (IL-12) through the acid-sensitive material mPEG-Dlinkm -PDLLA and low-temperature expansion effect of Pluronic F127. The nanoparticles encrich in the tumor site, significantly inhibit the growth and metastasis of breast cancer cells 4T1, and prolong the overall survival of tumor-bearing mice. The underlying immune mechanism is further explored. The combination of PTX and IL-12 activates T lymphocytes and NK cells to release IFN-γ, selectively inhibits regulatory T cells and induces M1-type differentiation of tumor-related macrophages, thereby improving tumor immunosuppressive microenvironments. This study may provide an effective strategy for cancer immunochemotherapy through co-delivery of chemotherapeutic drug and immune cytokine by the facile thermo-sponge nanoparticles.

A sequentially responsive and structure-transformable nanoparticle with a comprehensively improved 'CAPIR cascade' for enhanced antitumor effect.

An intravenously administered drug delivery system should undergo a five-step 'CAPIR' cascade (circulation, accumulation, penetration, internalization and release), and the maximal efficiency of each step is of great importance to obtain the improved final therapeutic benefits and overall survival rate. Here, a pH/matrix metalloproteinase-9 (MMP9) sequentially responsive and continuously structure-transformable nanoparticle assembled from a doxorubicin (DOX)-conjugated peptide was exploited for comprehensively improving the 'CAPIR cascade' and eventually enhancing the therapeutic efficacy. The chimeric peptide can self-assemble into spherical nanoparticles (RGD-sNPs) at pH 7.4 with a particle size of 45.7 ± 5.4 nm. By a combination of passive and active targeting mechanisms, RGD-sNPs achieved efficient accumulation at the tumor site (∼15.1% ID g-1 within 24 h). Both in vitro and in vivo experiments revealed that RGD-sNPs can be transformed into rod-like nanoparticles (S-NFs) triggered by MMP9 that overexpressed in the tumor microenvironment, demonstrating remarkable advantages of deep tumor penetration, prolonged drug retention with ∼3.7% ID g-1 at 96 h, and 2-fold enhanced internalization. Subsequently, S-NFs would respond to the intracellular weakly acidic stimuli to rapidly release DOX for induction of cytotoxicity and apoptosis. Meanwhile, the remaining peptide was further converted into long fibers (length >5 µm) with significant cytotoxicity, thereby exerting a synergistic antitumor effect. Thus RGD-sNPs displayed superior antitumor efficacy and extended the median survival period to 55 days. This provides a new horizon for the exploration of high-performance antitumor nanomedicines.

Selective self-induced stimulus amplification prodrug platform for inhibiting multidrug resistance and lung metastasis.

Tumor heterogeneity is considered as one of main obstacles to limit the clinical application of stimuli-responsive nanocarriers. Multidrug resistance (MDR) is also a major challenge in cancer chemotherapy. Here, we developed a tumor redox heterogeneity-responsive prodrug with self-induced reactive oxygen species (ROS) amplification property for facilitating rapid drug release and overcoming MDR and lung metastasis. The prodrug can self-assemble into polymer micelles (PMs) with high drug loading content (~30%), good physiological stability, prolonged systemic circulation and enhanced tumor distribution. Moreover, the prodrug PMs can stimulate tumor-specific ROS signal amplification, which provided a replenishment of consumed ROS necessary for rapid and complete drug release. The elevated ROS could not only evoke the mitochondria-dependent apoptosis by caspase-9/3 activation, but also inhibit inherent and acquired drug resistance by altering expression of Bcl-2 protein family and by reducing mitochondria membrane potential (ΔΨm) and ATP level in cancer cells. As a result, the prodrug PMs showed enhanced efficacy for inhibiting tumor growth in S180 sarcoma tumor model and in drug-resistant tumor model MCF-7/ADR and preventing lung metastasis in 4T1 in situ breast cancer model. This novel approach reported here may provide a promising strategy in the design of stimuli-responsive nanocarriers for efficient therapy of multidrug resistant and metastatic tumor.