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Abstract. Background:. There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. Methods:. In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. Results:. At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P

Abstract Introduction Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). Methods A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. Results In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. Conclusion Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

Abstract The Schizothoracinae fish are a natural group of cyprinids widely distributed in rivers and lakes in the Qinghai-Tibetan Plateau (QTP) and adjacent regions. These fish parallelly evolved with the QTP uplift and are thus important for uncovering geological history, the paleoclimatic environment, and the mechanisms of functional adaptation to environmental change. However, a dataset including species occurrences and functional traits, which are essential for resolving the above issues and guiding relevant conservation, remains unavailable. To fill this gap, we systematically compiled a comprehensive dataset on species occurrences and functional traits of Schizothoracinae fish from our long-term field samplings and various sources (e.g., publications and online databases). The dataset includes 7,333 occurrence records and 3,204 records of 32 functional traits covering all the genera and species of Schizothoracinae fish (i.e., 12 genera and 125 species or subspecies). Sampling records spanned over 180 years. This dataset will serve as a valuable resource for future research on the evolution, historical biogeography, responses to environmental change, and conservation of the Schizothoracinae fish.

Abstract Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.

Renal angiomyolipoma is a benign mesenchymal tumor that can be divided into classical and other subtypes. Angiomyolipoma with epithelial cysts (AMLEC) is an extremely rare non classical subtype. AMLEC without fat component is even rarer. We report a case of AMLEC without fat in a 29-year-old man who was provisionally diagnosed with cystic renal carcinoma by ultrasonography, abdominal enhanced CT and MRI. He had no complaints, or personal or family history of TSC, or other malignancies. Based on imaging findings, robot-assisted laparoscopic nephron-sparing partial nephrectomy through a retroperitoneal approach was performed for the purpose of both diagnosis and treatment. We diagnosed AMLEC after considering the differential diagnosis of other cystic renal neoplasms, such as cystic renal carcinoma, multilocular cystic renal cell neoplasm of low malignant potential, adult cystic nephroma and mixed epithelium and stromal tumor. Meanwhile, the whole-exon sequencing (WES) results showed insert-splicing mutation in the 21st exon and 20th exon of the TSC1 gene. No treatments were performed after the operation and no evidence of recurrence or metastasis at regular follow-up.

Abstract The emulation of human multisensory functions to construct artificial perception systems is an intriguing challenge for developing humanoid robotics and cross‐modal human–machine interfaces. Inspired by human multisensory signal generation and neuroplasticity‐based signal processing, here, an artificial perceptual neuro array with visual‐tactile sensing, processing, learning, and memory is demonstrated. The neuromorphic bimodal perception array compactly combines an artificial photoelectric synapse network and an integrated mechanoluminescent layer, endowing individual and synergistic plastic modulation of optical and mechanical information, including short‐term memory, long‐term memory, paired pulse facilitation, and “learning‐experience” behavior. Sequential or superimposed visual and tactile stimuli inputs can efficiently simulate the associative learning process of “Pavlov's dog”. The fusion of visual and tactile modulation enables enhanced memory of the stimulation image during the learning process. A machine‐learning algorithm is coupled with an artificial neural network for pattern recognition, achieving a recognition accuracy of 70% for bimodal training, which is higher than that obtained by unimodal training. In addition, the artificial perceptual neuron has a low energy consumption of ∼20 pJ. With its mechanical compliance and simple architecture, the neuromorphic bimodal perception array has promising applications in large‐scale cross‐modal interactions and high‐throughput intelligent perceptions.

There is sufficient evidence indicating that keloid is strongly associated with atopic dermatitis (AD) across ethnic groups. However, the molecular mechanism underlying the association is not fully understood. The aim of this study is to discover the underlying mechanism of the association between keloid and AD by integrating comprehensive bioinformatics techniques and machine learning methods. The gene expression profiles of keloid and AD were downloaded from the Gene Expression Omnibus (GEO) database. A total of 449 differentially expressed genes (DEGs) were found to be shared in keloid and AD using the training datasets of GEO (GSE158395 and GSE121212). The hub genes were identified using the protein-protein interaction network and Cytoscape software. 20 of the most significant hub genes were selected, which were mainly involved in the regulation of the inflammatory and immune response. Through two machine learning algorithms of LASSO and SVM-RFE, CCR5 was identified as the most important key gene. Subsequently, upregulated CCR5 gene expression was confirmed in validation GEO datasets (GSE188952 and GSE32924) and clinical samples of keloid and AD. Immune infiltration analysis showed that T helper (Th) 1, 2 and 17 cells were significantly enriched in the microenvironment of both keloid and AD. Positive correlations were found between CCR5 and Th1, Th2 and Th17 cells. Finally, two TFs of CCR5, NR3C2 and YY1, were identified, both of which were downregulated in keloid and AD tissues. Our study firstly reveals that keloid and AD shared common inflammatory and immune pathways. Moreover, CCR5 plays a key role in the pathogenesis association between keloid and AD. The common pathways and key genes may shed light on further mechanism research and targeted therapy, and may provide therapeutic interventions of keloid with AD.

Many skin diseases, such as atopic dermatitis (AD), are featured with the dysbiosis of skin microbiota. The clinically recommended options for AD treatments suffer from poor outcomes and high side-effects, leading to severe quality-of-life impairment. To deal with this long-term challenge, we develop a living bacterial formulation (Hy@Rm) that integrates skin symbiotic bacteria of Roseomonas mucosa with poly(vinyl pyrrolidone), poly(vinyl alcohol) and sodium alginate into a skin dressing by virtue of the Ca2+-mediated cross-linking and the freezing-thawing (F-T) cycle method. Hy@Rm dressing creates a favorable condition to not only serve as extrinsic culture harbors but also as nutrient suppliers to support R. mucosa survival in the harsh microenvironment of AD sites to defeat S. aureus, which predominantly colonizes AD skins as an indigenous pathogen, mainly through the secretion of sphingolipids metabolites by R. mucosa like a therapeutics bio-factory. Meanwhile, this elaborately designed skin dressing could accelerate wound healing, normalize aberrant skin characters, recover skin barrier functions, alleviate AD-associated immune/inflammation responses, functioning like a combinational therapy. This study offers a promising means for the topical bacteria transplant to realize effective microbe biotherapy toward the skin diseases feature with microbe milieu disorders, including but not limited to AD disease.

The enzyme catalysis conversion of lignocellulosic biomass into valuable chemicals and fuels showed a bright outlook for replacing fossil resources. However, the high cost and easy deactivation of free enzymes restrict the conversion process. Immobilization of enzymes in metal–organic frameworks (MOFs) is one of the most promising strategies due to MOF materials’ tunable building units, multiple pore structures, and excellent biocompatibility. Also, MOFs are ideal support materials and could enhance the stability and reusability of enzymes. In this paper, recent progress on the conversion of cellulose, hemicellulose, and lignin by MOF-immobilized enzymes is extensively reviewed. This paper focuses on the immobilized enzyme performances and enzymatic mechanism. Finally, the challenges of the conversion of lignocellulosic biomass by MOF-immobilized enzyme are discussed.

Abstract Cutaneous melanoma (CM, hereafter referred to as melanoma) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in melanoma has not been fully elucidated. In this study, we examined the relationship between pyroptosis and the prognosis of melanoma through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with melanoma prognosis. A higher pyroptosis score was associated with a more favorable overall survival. We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively evaluate the prognosis of melanoma. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4+ T cells, CD8+ T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of melanoma to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified solute carrier family 31 member 2 (SLC31A2) and collagen type 4 alpha 5 chain (COL4A5) as being associated with resistance to most of these drugs. In conclusion, this PGS is an effective and novelty prognostic indicator in melanoma, and also has an association with the melanoma immune microenvironment and melanoma treatment decision-making.

Abstract Background Renal cell carcinoma (RCC) with haemangioblastoma-like characteristics is a type of RCC reported in recent years. RCC with (angio) leiomyomatous stroma (RCCLMS) was included as a provisional entity of the 2016 World Health Organization (WHO) classification. RCC with haemangioblastoma-like characteristics and leiomyomatous stroma is extremely rare. This is the first report of a rare tumour harbouring TSC2 and SETD2 variations. Case presentation The patient was a 38-year-old woman who presented with discomfort in the area of her right kidney. Ultrasound and enhanced CT showed a right renal mass, and clear cell renal cell carcinoma (CCRCC) was suspected; hence, robot-assisted laparoscopic nephron-sparing partial nephrectomy was performed. Gross examination revealed a well-circumscribed tumour measuring 2.0 cm × 1 cm × 0.7 cm under the renal capsule adjacent to the stripping edge that was greyish yellow and greyish red in colour. Histologic examination showed that the tumour consisted of three different structures: a CCRCC-like region, a haemangioblastoma-like region, and a focal leiomyomatous stroma component. Based on immunohistochemistry, the CCRCC-like region was diffusely strongly positive for AE1/AE3, vimentin, CAIX, PAX8, PAX2, CK7, and CAM5.2, partly positive for HNF1α, and negative for CD10, α-inhibin, NSE, S-100, CD34, and TFE3. The haemangioblastoma-like area was diffusely positive for vimentin, CAIX; partly positive for PAX8, PAX2, α-inhibin, and S-100; mostly positive for NSE; and slightly positive for HNF1α; the CD34 staining highlighted the complex capillary network. The Ki67 index was approximately 1–2% in the two above areas, and the leiomyomatous stroma was strongly positive for SMA. The whole-exon sequencing (WES) showed TSC2 and SETD2 variations. There was no progression after 18 months of follow-up. Conclusion We report for the first time a unique case of RCC with haemangioblastoma-like features and leiomyomatous stroma accompanied by rare molecular abnormalities. Whether this is a new tumour entity or a variant of clear cell carcinoma remains to be determined. The biological behaviour and clinical characteristics need to be further examined.

Abstract Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout (EpiCD147-OE or EpiCD147-KO) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis (EpiCD147-OE) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in EpiCD147-OE transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in EpiCD147-OE transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of CD147D207-230. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway.

Abstract Studies on clinical features of systemic lupus erythematosus among different age-onset patients are lacking in China. This multicentre study aimed to systemically compare clinical manifestations, comorbidities, organ involvement, and laboratory findings among 797 Chinese juvenile-onset, adult-onset, and late-onset SLE (JSLE, ASLE, and LSLE) patients. They were classified into JSLE, ASLE, and LSLE groups if first diagnosed at < 18, 18–50, and > 50 years old, respectively. Chi-square test and analysis of variance were employed for categorical and continuous variables respectively. In younger-onset patients, the SLE Disease Activity Index 2000 score was significantly higher (JSLE vs. ASLE vs. LSLE = 17.43 ± 9.139 vs. 16.34 ± 8.163 vs. 14.08 ± 6.474, p = 0.031). Mucocutaneous symptoms (79.5% vs. 73.4% vs. 62.0%, p = 0.042), especially malar rash (76.1% vs. 66.1% vs. 53.5%, p = 0.011) occurred more frequently, and proteinuria rate was higher (54.5% vs. 56.3% vs. 36.6%, p = 0.007). In later-onset patients, cardiopulmonary involvement increased (11.4% vs. 24.3% vs. 29.6%, p = 0.012). In ASLE, hypoalbuminemia rate elevated (46.6% vs. 59.9% vs. 47.9%, p = 0.015). Our study demonstrated in a Chinese population that JSLE may be more active and suffer mucocutaneous disorders, while LSLE tended to suffer cardiopulmonary involvement at-onset. These findings may help identify treatment priorities when facing different age-onset SLE patients.

Abstract. Background:. Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population. Methods:. This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria. Results:. In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals (P

Abstract Background Hematoporphyrin monomethyl Ether‐mediated photodynamic therapy (HMME‐PDT) is an effective and safe treatment option for patients with port‐wine stain (PWS) and might be an alternative approach for treating PWS. The data of long‐term follow‐up of HMME‐mediated PDT are limited. Objective We aimed to evaluate the current skin lesions of patients who underwent HMME‐PDT 10 years ago, and to compare the pre and post HMME‐PDT response with that at year 10 after this treatment. Method This is a retrospective study of PWS patients treated by HMME‐PDT. HMME‐PDT was carried out by a combination of hematoporphyrin monomethyl ether and 532‐nm continuous wave lasers. Clinical outcomes were graded by clinician‐evaluators based on before and after photographs of the lesion area to the following four‐level scale: no improvement, some improvement, great improvement or nearly complete remission. Results There was no obvious recurrence in the completely blanched area. However, the lesions became darkened and thicker in untreated areas. There was no long‐term side effect at the treatment site in all patients. Conclusion HMME‐PDT may be considered an effective alternative for the treatment of PWS. Its potential should be emphasized due to the relatively stable results shown in the long term.

ABSTRACT: Utilizing photothermal hydrogels as a wound dressing is a promising strategy to accelerate wound healing. Usually, a photothermal hydrogel has a strong light-absorbing capability, and hence its transparency can be largely sacrificed, which is unbeneficial for the visual monitoring of wound states. It remains challenging to balance the trade-off between the photothermal conversion and wound visualization for the photothermal hydrogel dressing. Herein, a composite photothermal hydrogel film with high transparency is presented for the visual monitor of the wound, which is constructed by incorporating CsxWO3 nanorods into the networks of polyacrylamide hydrogels. The composite photothermal hydrogel film exhibits high light absorption in the near-infrared region and high transmittance in the visible light region. Under 980 nm laser irradiation, the composite hydrogel can be heated up to 45 °C. In vivo animal experiment on mouse skin wound model shows that the composite hydrogel film can locally heat the skin wound to accelerate healing while maintaining more than 70% transparency to realize real-time observation of the wound. This study provides the first attempt to solve the problem of opacity in photothermal hydrogel dressings, promoting the possibility of its clinical applications.

The secreted form of 78-kDa glucose-regulated protein (sGRP78) has been widely reported for its property in aiding resolution of inflammatory. However, little is known on its potential in the treatment of colitis. To investigate the expression pattern and functional outcome of GRP78 in ulcerative colitis, its expression was measured in human and murine colitis samples. It was found that GRP78 was spontaneously secreted to a high level in gut, which is a physiological site of immune tolerance. During the active phase of DSS-induced colitis, the sGRP78 level was significantly reduced but rebounded quickly during resolving phase, making it a potential candidate for the treatment of colitis. In the following experiments, the administration of sGRP78 was proved to decrease susceptibility to experimental colitis, as indicated by an overall improvement of intestinal symptoms, restoration of TJ integrity, decreased infiltration of immune cells and impaired production of inflammatory cytokines. And specific cleavage of endogenous sGRP78 could aggravate DSS colitis. Adoptive transfer of sGRP78-conditioned BMDMs reduced inflammation in the gut. We linked sGRP78 treatment with altered macrophage biology and skewed macrophage polarization by inhibiting the TLR4-dependent MAP-kinases and NF-κB pathways. Based on these studies, as a naturally occurring immunomodulatory molecule, sGRP78 might be an attractive novel therapeutic agent for acute intestinal inflammation.

T helper type 17 (Th17) cell which is induced by interleukine-6 (IL-6)-signal transducers and activators of transcription 3 (STAT3) signaling is a central pro-inflammatory T cell subtype in rheumatoid arthritis (RA) and could be significantly reduced by paeoniflorin-6′-O-benzene sulfonate (CP-25) treatment with unclear mechanisms. This study was aimed to found out the mechanism of CP-25 in hampering Th17 cells differentiation in arthritic animals thus explore more therapeutic targets for RA. In mice with collagen-induced arthritis (CIA), both circulating and splenic Th17 subsets were expanded with increased STAT3 phosphorylation and decreased Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1)-β-arrestin2 (arrb2)-STAT3 interaction in CD4+ helper T (Th) cells. Either CP-25 or paroxetine (PAR), an established G protein coupled receptor kinase 2 (GRK2) inhibitor treatment effectively relieved the joints inflammation of CIA mice with substantially reduced Th17 cell population through inhibiting STAT3 and restoring the SHP1-arrb2-STAT3 complex. Knockout of arrb2 exacerbated the clinical manifestations of collagen antibody-induced arthritis with upregulated Th17 cells. In vitro studies revealed that depletion of arrb2 or inhibition of SHP1 promoted Th17 cell differentiation. Moreover, stimulation of adenosine A3 receptor (A3AR) simultaneously promoted Th17 cell differentiation via accelerating abbr2-A3AR binding, which could be prevented through inhibiting GRK2 phosphorylation by CP-25 or PAR, or genetically reducing GRK2. This work has demonstrated that CP-25 or PAR treatment recovers the SHP1-arrb2-STAT3 complex which prevents STAT3 activation in Th cells through reducing arrb2 recruitment to A3AR by inhibiting GRK2 phosphorylation, leading to the reduction in Th17 cell differentiation and arthritis attenuation.

Abstract Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

Nanomedicine has demonstrated great potential in enhancing cancer immunotherapy. However, nanoparticle (NP)-based immunotherapy still has limitations in inducing effective antitumor responses and inhibiting tumor metastasis. Herein, polyethylenimine (PEI) hybrid thin shell hollow mesoporous silica NPs (THMSNs) were applied as adjuvant-nanocarriers and encapsulated with very small dose of photosensitizer chlorine e6 (Ce6) to realize the synergy of photodynamic therapy (PDT)/immunotherapy. Through PEI etching, the obtained Ce6@THMSNs exhibited enhanced cellular internalization and endosome/lysosome escape, which further improved the PDT efficacy of Ce6@THMSNs in destroying tumor cells. After PDT treatment, the released tumor-associated antigens with the help of THMSNs as adjuvants promoted dendritic cells maturation, which further boosted CD8+ cytotoxic T lymphocytes activation and triggered antitumor immune responses. The in vivo experiments demonstrated the significant potency of Ce6@THMSNs-based PDT in obliterating primary tumors and inducing persistent tumor-specific immune responses, thus preventing distant metastasis. Therefore, we offer a THMSNs-mediated and PDT-triggered nanotherapeutic system with immunogenic property, which can elicit robust antitumor immunity and is promising for future clinical development of immunotherapy.

Abstract Photodynamic therapy (PDT) is an emerging technique for treating tumors. Especially, topical administration of photosensitizers (PSs) is more favorable for superficial tumor treatments with low systematic phototoxicity. Yet, ineffective migration of PSs to targeted tumor tissues and rapid consumption of O2 during PDT greatly limit their effects. Herein, PS‐loaded microneedle (MN) patches with O2 propellant for a deeper and faster transdermal delivery of PS and improved PDT by embedding sodium percarbonate (SPC) into dissolving poly(vinyl pyrrolidone) MNs are presented. It is shown that SPC in the MNs can react with surrounding fluid to generate gaseous oxygen bubbles, forming vigorous fluid flows and thus greatly enhancing PS of chlorin e6 (Ce6) penetration in both hydrogel models and skin tissues. Reactive oxygen species (ROS) in hypoxic breast cancer cells (4T1 cells) are greatly increased by rapid penetration of PS and relief of hypoxia in vitro, and Ce6‐loaded SPC MNs show an excellent cell‐killing effect. Moreover, lower tumor growth rate and tumor mass after a 20‐d treatment in tumor‐bearing mice model verify the improved PDT in gaseous oxygen‐droved delivery of PS. This study demonstrates a facile yet effective route of MN delivery of PSs for improved PDT in hypoxic tumor treatment.

Abstract. Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

BackgroundThe aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status.MethodsIn this study, based on 1999–2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients’ survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression.ResultsThe overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment.ConclusionsThe proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Designing efficient radio frequency antenna for wireless stretchable multifunction electronics remains a challenge. Here, the authors present epidermal radio frequency antenna based on silver nanofibers network for wireless power transfer and information identification.

Abstract. Allergic contact dermatitis is a common clinical allergic disease. The patch test is the gold standard for finding and clarifying contact allergens. With the deepening understanding of the epidemiology, pathogenesis, and clinical manifestations of contact dermatitis, as well as the increased requirements for the standardized application of patch tests, the relevant consensus needs to be continuously updated. This consensus is updated on the basis of the version issued in 2015. In this revised version, it refines the selection of clinical indications, improves the judgment and interpretation of results, adds delayed detection and patient education, and so on, which aims to further standardize clinical applications and improve the value of patch test.

Background: The prevalence and health-related quality of life of skin disease have been understudied in adolescents. Objective: To investigate the prevalence and relevant patient-reported outcomes of noncommunicable skin diseases in college students. Methods: First-year college students from 5 universities in China were investigated in the cross-sectional study. Skin diseases were diagnosed by dermatologists in the field survey. Itch and pain, symptoms of depression and anxiety, and sleep quality were measured by validated tools. Results: A total of 28,364 students consented to participate and completed the survey. The prevalence of acne, eczema, chronic urticaria, psoriasis, and vitiligo was 10.3%, 5.8%, 2.6%, 0.16%, and 0.23%, respectively. Eczema and chronic urticaria were associated with lower health utility estimates. Most diseases, but not psoriasis and vitiligo, were associated with the symptoms of depression and sleep disturbance. Itch intensity predicted other patient-reported outcome scores better in healthy controls than in individuals with skin diseases. Sex difference in the associations of skin diseases with patient-reported outcomes was not identified. Limitations: Cross-sectional study design and limited generalizability to the nonstudent population. Conclusion: Skin diseases are associated with moderately impaired emotional well-being, sleep quality, and quality of life, partly attributable to cutaneous symptoms.

Abstract Background This study aimed to assess the independent prognostic value of tumor size compared with other clinical and pathologic features of primary invasive cutaneous melanoma (CM). Methods This study included 28,593 patients with primary invasive CM in Surveillance, Epidemiology, and End Results Program database diagnosed from 2004 through 2016. Tumor size was divided into five subgroups (≤6, 7‐12, 13‐30, 31‐42, and >42 mm). The primary endpoint was melanoma‐specific survival (MSS). Results The relationship between tumor size and survival was piecewise. After adjusting for age, sex, primary site, histopathologic cell type, Breslow thickness, ulceration, mitotic rate, regional metastasis, and distant metastasis, the hazard ratio (HR) of MSS increased with increasing tumor size until a peak at 31‐42 mm (HRs, 1.33, 1.59, 2.41, respectively; all P 42 mm subgroup had the shortest MSS in T4. In addition, tumor size with a cutoff value of 12 mm showed stronger prognostic value for MSS (HR, 2.32; 95% CI, 1.80‐2.98; P

Abstract Background Melanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment. Methods We detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma. Results We found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis. Conclusions Taken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment.

Objective This study analyzed the associations of different crescents’ fraction and clinical features in a Chinese lupus nephritis cohort based on the 2018 revision of ISN/RPS classification system. Methods A total of 288 lupus nephritis patients with complete clinicopathological data and well follow-up was enrolled. The fraction of glomeruli with cellular or fibrocellular crescents based on the new system was reevaluated. The association between crescents fractions and the outcomes were further analyzed. Results The median follow-up period was 76.5 months. Cellular or fibrocellular crescents were present in 146 (50.7%) of the total individuals. The percentage of crescents were significantly associated with severe clinical renal injury indices and other renal pathological parameter. According to the survival receiver operating characteristic (survival ROC) curve, the optimal cutoff level of cellular or fibrocellular crescents for predicting the composite events was 7.39%. By multivariable Cox hazard analysis, the presence of crescents was predictive of survival from the composite events with a hazard ratio [HR] of 2.5 (95% CI 1.190–5.431; p = .02). Furthermore, when we used absent, present in less than 7.39% of glomeruli, and present in greater than or equal to 7.39% of glomeruli as cutoffs in all the patients, a gradation appeared, with adjusted HRs of 2.9 (95% CI 1.326–6.313; p = .008) for crescents in greater than or equal to 7.39% of glomeruli, in reference to no crescents. Conclusion We proposed that the crescents were not uncommon and had important clinical significance in lupus nephritis. The cutoff point of crescents as prognosticator might be nearly 7.39%.

For weakly basic drugs, the sharp decrease of drug solubility and the following drug precipitation after drugs transferring from the gastric fluid to the intestinal fluid in the gastrointestinal (GI) tract is a main reason for the poor oral bioavailability of drugs. Here, an anticoagulant dabigatran etexilate (DE) was used as a model drug, and a composite nanocarrier system of DE was developed to improve the drug dissolution by decreasing the drug leakage in the stomach and inhibiting the drug precipitation in the intestinal tract. With the encapsulation of drugs in nanocarriers, the precipitation percentage of DE in composite nanocarriers was 22.25 ± 3.88% in simulated intestinal fluid, which was far below that of the commercial formulation. Moreover, the relative bioavailability of DE-loaded composite nanocarriers (456.58%) was greatly enhanced and the peak of its activated partial thromboplastin time was also significantly prolonged (p

Objectives Vaccinations can prevent COVID-19 and control its spread quickly and efficiently. This study aimed to investigate knowledge and willingness of geriatric care facility staff to receive a COVID-19 vaccine, and to provide a basis for the government to promote the COVID-19 vaccine and guide people to get vaccinated. Study design A cross-sectional study. Methods Data on characteristics of the participants, knowledge about the COVID-19 vaccine, and willingness to get vaccinated for COVID-19 were collected through an online survey from May 19 to June 18, 2021. Statistical analyses were conducted with ANOVA, chi-square, logistic regression. Results The survey illustrated that the highest score of COVID-19 vaccine knowledge was 50, the lowest 20, and the average 44.22. It also demonstrated that 91.3% of the participants had a good knowledge of COVID-19 vaccine, and that 97.3% participants were willing to receive the COVID-19 vaccine. The results showed that geriatric care facility staff had varied level of the COVID-19 vaccine knowledge depending upon their age, educational background, and other factors, and correspondingly, their willingness to receive COVID-19 vaccine was affected by their knowledge level of COVID-19 vaccine. Conclusions In general, the participants, the staff of geriatric care facilities in Anhui Province, had good mastery of the COVID-19 vaccine, and they were willing to get vaccinated. However, there still existed a few participants with poor knowledge, who were unwilling to get vaccinated against COVID-19. Government can guide people to accept vaccination by enhancing publicity about the effects and adverse reactions of COVID-19 vaccines.

Psoriasis is a common chronic inflammatory skin disease mainly characterized by keratinocyte hyperproliferation and massive infiltration of inflammatory immune cells. Acitretin (ACT), an FDA-approved first-line systemic drug for psoriasis treatment, could suppress the proliferation of keratinocytes and downregulate the expression of inflammatory cytokines by modulating signal transducer and activator of transcription (STAT) signaling pathways. However, dose-dependent side effects of ACT limit its long-term administration in the clinic. Therefore, improving the therapeutic efficacy of ACT to reduce clinical dosage will benefit the patients. Here, we develop ACT-conjugated dextran nanoparticles (ACT-Dex NPs) and evaluated the potential for psoriasis treatment. Our results indicate that ACT-Dex NPs ameliorate psoriasis-like skin disease significantly at a low dosage which does not cause side effects, while neat ACT drugs at an equivalent dosage provide much less benefit. Moreover, we demonstrate that ACT-Dex NPs suppress keratinocyte proliferation more efficiently than neat ACT by enhancing the inhibitory effect on STAT3 phosphorylation. Thus, the proposed ACT-Dex NPs provide an effective and safe option for psoriasis treatment.

Purpose: Night shift work is common in the current working environment and is a risk factor for many diseases. The study aimed to explore the relationship between night shift work with chronic spontaneous urticaria (CSU), and the modification effect of circadian dysfunction on it.Methods: A cross-sectional survey was conducted among Chinese workers. Exposure was measured by night work history and duration. Circadian dysfunction was characterized by excessive daytime sleepiness (EDS). The diagnosis of CSU was made by dermatologists who were investigating on the spot. The effect size was expressed as odds ratios (ORs).Results: A total of 8,057 participants were recruited, and 7,411 (92%) with complete information were included in the final analyses. The prevalence rates of CSU for workers without night shift and those with night shift history were 0.73 and 1.28%, respectively. Compared with workers who never worked night shifts, the risk of CSU increased with the length of night shift work: OR = 1.55 (95% confidence interval [CI]: 0.78–3.06) for duration

Objective: The effect of processed foods on atopic dermatitis (AD) in adults is unclear. This study was to evaluate the association between processed foods and AD in the Chinese adult population.Design: This study included three population-based cross-sectional studies using cluster sampling by villages, institutions, or factories. Participants underwent dermatological examinations by certificated dermatologists and a food frequency questionnaire survey. A spot urine sample was collected to estimate the daily sodium intake. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were presented as the effect size.Setting: Shiyan city of Hubei province, and Huayuan, Shimen, Hengyang, Zhuzhou, and Changsha of Hunan province.Participants: Automobile manufacture workers from Shiyan of Hubei province, and rural residents and civil servants from Hunan.Results: A total of 15,062 participants, including 3,781 rural residents, 5,111 civil servants, and 6,170 workers, completed all evaluations. Compared to those hardly consumed pickles, consumption of pickles 1–3 times per week was significantly associated with AD (aOR: 1.35; 95% CI: 1.06–1.70). The intake of processed meats 1–3 times per month (aOR: 1.29; 95% CI: 1.05–1.58) and 1–3 times per week (aOR: 1.44; 95% CI: 1.11–1.87) were associated with AD dose-dependently when compared with those who rarely ate processed meats. Compared with non-consumers, the consumption of any processed foods 1–3 times per week (aOR: 1.39; 95% CI: 1.08–1.80) and ≥4 times per week (aOR: 1.41; 95% CI: 1.05–1.89) showed increased risks of AD. A positive association of estimated sodium intake with AD was also observed.Conclusion: Intake of processed foods is associated with AD in Chinese adults.

Background Overuse and misuse of antibiotics is a public health problem in low-income and middle-income countries. Although the association of antibiotics with atopic and allergic diseases has been established, most studies focused on prenatal exposure and the occurrence of disease in infants or young children.Objective To investigate the association of preschool use of antibiotics with atopic and allergic skin diseases in young adulthood.Design Population-based retrospective cohort.Setting and participants The first-year college students (n=20 123) from five universities were investigated. The sampled universities are located in Changsha, Wuhan, Xiamen, Urumqi and Hohhot, respectively.Methods We conducted a dermatological field examination and a questionnaire survey inquiring the participants about the frequency of upper respiratory tract infection (URTI) and the preschool antibiotics use (prior to 7 years old). The two-level probit model was used to estimate the associations, and adjusted risk ratio (aRR) and 95% CI were presented as the effect size.Results A total of 20 123 participants with complete information was included in the final analysis. The frequent antibiotics use intravenously (aRR 1.36, 95% CI 1.14 to 1.62) and orally (aRR 1.18, 95% CI 1.01 to 1.38) prior to 7 years old was significantly associated with atopic dermatitis in young adulthood. Similar trends could be observed in allergic skin diseases among those who use antibiotics orally and intravenously, with RRs of 1.16 (95% CI 1.01 to 1.34) and 1.33 (95% CI 1.13 to 1.57), respectively.Conclusions Preschool URTI and antibiotics use significantly increases the risk of atopic and allergic skin diseases in young adulthood.

Land use in the uplands can substantially impact the biological community in stream ecosystems, but how the trophic structure of aquatic communities within riverine food webs respond to catchment land use changes within their respective catchment remains unclear. Here, we investigated the impact of land use on aquatic communities in two streams in subtropical China. We measured isotopic compositions of basal resources, four macroinvertebrate functional feeding groups (scrapers, collectors, shredders, and predators with 132 taxa), and three fish functional feeding groups (herbivores, omnivores, and piscivores with 26 species) in three land uses (woodland, agricultural, and urban). Isotopic values of δ13C and δ15N were used to estimate the dietary proportions of consumers (macroinvertebrates and fish) and community-level metrics (niche width and trophic diversity). We found that isotopic values of basal resources, macroinvertebrates, and fish varied significantly among sampling sites adjacent to the three land uses. Dietary analysis showed that terrestrial resources contributed relatively less (~20%) than aquatic resources to consumers (macroinvertebrates and fish) in higher trophic levels, especially in the urban sites. Compared to woodland sites, food webs in the urban sites had lower niche width and higher trophic redundancy, and agricultural sites had higher trophic length and lower niche width. Trophic structure alterations in response to land use primarily resulted from availability and variability of basal resources in the upstream river channel and the riparian zone, and also the feeding plasticity of macroinvertebrates and/or fish. These empirical findings indicate the importance of diversity across all trophic levels in the management of stream ecosystems in urban and agricultural landscapes.

The piezophototronic effect is the coupling of piezoelectricity, semiconductor behavior and photon excitation in wurtzite materials, which can enhance the performance of optoelectronic nano‐devices by regulating a series of processes of carrier injection, transport, and recombination. In recent years, many research results have been reported on the improvement of nanophotoelectric nano‐device efficiency by piezophototronic effect, such as photovoltaic devices, light‐emitting devices, transistors, etc. Herein, the research results of piezophototronic effect in the field of nanosensors, including enhancing the performance of traditional nanosensors and new types of pressure/deformation/tactile sensors based on piezophototronic effect are comprehensively summarized. Finally, the future development of piezophototronic effect in the field of nanosensors is discussed.

Abstract Background The downstream targets of farnesoid X receptor (FXR) such as miRNAs have a potent effect on the progression of many types of cancer. We aim to study the effects of FXR on osteosarcoma (OS) development and the potential role of microRNA-23b-3p. Methods The expressions of FXR and miR-23b-3p in normal osteoblasts and five osteosarcoma cell lines were measured. Their correlations were analyzed by Pearson’s test and verified by the introduction of FXR agonist, GW4064. TargetScan predicted that cyclin G1 (CCNG1) was a target for miR-23b-3p. The transfection of FXR siRNA was performed to confirm the correlation between FXR and miR-23b-3p. We further transfected miR-23b-3p inhibitor into MG-63 cells, and the transfected cells were treated with 5 μM GW4064 for 48 h. Quantitative PCR (qPCR) and Western blot were performed for expression analysis. Cell proliferation, cell apoptosis rate, and cell cycle distribution were assessed by clone formation assay and flow cytometry. Results Scatter plot showed a positive correlation between FXR and miR-23b-3p (Pearson’s coefficient test R 2 = 1.00, P = 0.0028). As CCNG1 is a target for miR-23b-3p, the treatment of GW4064 induced the downregulation of CCNG1 through upregulating miR-23b-3p. The inhibition of miR-23b-3p obviously promoted cell viability, proliferation, and cell cycle progression but reduced apoptosis rate of MG-63 cells; however, the treatment of GW4064 could partially reverse the effects of the inhibition of miR-23b-3p on OS cells. Conclusions Upregulated FXR by GW4064 can obviously suppress OS cell development, and the suppressive effects may rely on miR-23b-3p/CCNG1 pathway.

Objectives: It is understudied how frequently adolescents use nutritional supplements (NS) and whether the corresponding behavior is associated with skin diseases that may cause unpleasant symptoms and disfigurement. The current study aimed to investigate the prevalence of NS use in Chinese college students and its association with inflammatory skin diseases.Methods: This was a university-based epidemiologic investigation that included 20,138 students who underwent dermatological examinations. A questionnaire survey was conducted to inquire about the use of NS along with related information. Skin diseases were diagnosed by dermatologists during the health examination. Logistic regression models were used for analysis. Adjusted odds ratios (aORs) were presented as the effect size.Results: Survey responses from a total of 20,138 participants were analyzed. Specifically, 18.3% of the participants reported the use of NS in the past year. The use of vitamin C was most frequently reported, accounting for a proportion of 12.9%, followed by vitamin B and mineral supplements. The use of NS was found to be associated with female sex, Han ethnicity, higher annual household income, and a series of healthy lifestyles such as more physical activity, less second-hand smoke exposure, less alcohol consumption, and higher intake of milk and yogurt (p < 0.001). Participants with chronic urticaria (aOR = 1.3; 95% CI, 1.0–1.7), atopic dermatitis (aOR = 1.4; 95% CI, 1.2–1.6), or acne (aOR = 1.17; 95% CI, 1.04–1.31) were more likely to use NS, especially herbs (aOR = 2.7; 95% CI, 1.2–3.7), followed by vitamin B (aOR = 1.6; 95% CI, 1.2–2.0) and mineral supplements (aOR = 1.4; 95% CI, 1.0–2.0).Conclusion: College students with inflammatory skin diseases are more likely to use NS.

Global climate change is increasingly and profoundly threatening fishes, resulting in an uncertain future for both wild fish diversity and global fisheries. Understanding how fish growth responds to changing environments is essential for indicating and predicting the impacts of climate change on fish populations, communities, and even aquatic ecosystems, but the knowledge on this topic remains incomplete, and some findings are contradictory. This study aimed to review the status of current research by analysing data on the environment, species, and response patterns from 1187 documents published from 1976 to 2018, which helped to identify key questions that are currently neglected and potential reasons for these divergences. The results found that 75% of studies were conducted in the field (mostly in temperate and subtropical zones), while the remainder were controlled experiments. Fishes from freshwater ecosystems were relatively less studied than their marine counterparts. Less than 1% of the recorded fish species (309 vs. approximately 35,000) from 30 orders have been studied to examine their growth responses to climate change. All studied fishes were from Actinopterygii. The top three orders were Perciformes, Cypriniformes, and Salmoniformes by species number, while Salmoniformes was the most frequently studied order. The most common habitat type of the studied fish was pelagic, followed by demersal and reef-associated habitats. Small fishes were relatively undervalued in both marine and freshwater systems. The mean trophic levels of the studied species were 3.2 for freshwater fish and 3.4 for marine fish. Carnivores were the dominant trophic guild studied in both marine and freshwater systems. The overall effects of climate change (primarily temperature variables) on fish growth (reflected in physiology and health) were negative at both the global and local scales. Therefore, the results suggested that future studies covering more species (e.g., chondrichthyan fishes, low-level consumers, and small fishes) and areas (e.g., high-latitude areas) are required to obtain a better understanding of climate change impacts on fish growth.

Abstract Immune checkpoints blockades have shown promising clinical effects in various malignancies, but the overall response rate is low. Here, the immune features are comprehensively characterized in >10 000 cancer patients from The Cancer Genome Atlas and significantly positive correlations are observed between targets of Sunitinib and inhibitory immune checkpoints and suppressive immune cells. It is further confirmed that Sunitinib treatment increases the antitumor immunity in a phase III trial. Mechanistically, it is discovered that Sunitinib regulates the stability of tumor PD‐L1 via p62, that p62 can bind to PD‐L1 and specifically promote its translocation into autophagic lysosome for degradation. Preclinically, Sunitinib shows a synergistic antitumor effect with cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) monoclonal antibody (mAb) in melanoma and nonsmall cell lung cancer (NSCLC) immune competent mice by promoting the tumor‐infiltrating lymphocytes activity. Clinically, a higher PD‐L1 level but a lower p62 level in the tumor region of responders as compared to those of nonresponders among anti‐PD‐1‐treated NSCLC patients is observed. Taken together, by utilizing rigorous computational analysis, functional characterization in vitro and in vivo, and neoadjuvent clinical trial, a novel molecular mechanism is revealed regarding the regulation of PD‐L1 via p62, thus providing a novel therapeutic strategy by the combination treatment of CTLA‐4 with Sunitinib.

The COVID-19 outbreak caused by SARS-CoV-2 challenges the medical system by interfering with routine therapies for many patients with chronic diseases. In patients with cancer receiving immune checkpoint inhibitors (ICIs), difficulties also arise from the incomplete understanding of the intricate interplay between their routine treatment and pathogenesis of the novel virus. By referring to previous ICI-based investigations, we speculate that ICIs themselves are not linked to high-infection risks of respiratory diseases or inflammation-related adverse effects in patients with cancer. Moreover, ICI treatment may even enhance coronavirus clearance in some patients with malignant tumor by boosting antiviral T-cell responsiveness. However, the ‘explosive’ inflammation during COVID-19 in some ICI-treated patients with cancer was illustrated as exuberant immunopathological damage or even death. In case of the COVID-19 immunopathogenesis fueled by ICIs, we propose a regular monitor of pathogenic T-cell subsets and their exhaustion marker expression (eg, Th17 and interleukin (IL)-6-producing Th1 subsets with surface programmed death 1 expression) to guide the usage of ICI. Here we aimed to address these considerations, based on available literature and experience from our practice, that may assist with the decision-making of ICI administration during the pandemic.

Abstract Background Vitex negundo L (Verbenaceae) is an aromatic shrub that is abundant in Asian countries. A series of compounds from Vitex negundo have been used in traditional Chinese medicine for the treatment of various diseases. Cutaneous melanoma is one of the most aggressive malignancies. A significant feature of melanoma is its resistance to traditional chemotherapy and radiotherapy; therefore, there is an urgent need to develop novel treatments for melanoma. Methods We first examined the effects of VB1 (vitexin compound 1) on cell viability by CCK-8 (cell counting kit) and Colony Formation Assay; And then, we analyzed the apoptosis and cell cycle by flow cytometry, verified apoptosis by Immunoblotting. The in vivo effect of VB1 was evaluated in xenograft mouse model. Potential mechanisms of VB1’s antitumor effects were explored by RNA sequencing and the key differential expression genes were validated by real-time quantitative PCR. Finally, the intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and the DNA damage was revealed by Immunofluorescence and Immunoblotting. Results In this study, we show that VB1, which is a compound purified from the seed of the Chinese herb Vitex negundo, blocks melanoma cells growth in vitro and in vivo, arrests the cell cycle in G2/M phase and induces apoptosis in melanoma cell lines, whereas the effects are not significantly observed in normal cells. To study the details of VB1, we analyzed the alteration of gene expression profiles after treatment with VB1 in melanoma cells. The findings showed that VB1 can affect various pathways, including p53, apoptosis and the cell cycle pathway, in a variety of melanoma cell lines. Furthermore, we confirmed that VB1 restored the P53 pathway protein level, and then we demonstrated that VB1 significantly induced the accumulation of ROS, which resulted in DNA damage in melanoma cell lines. Interestingly, our results showed that VB1 also increased the ROS levels in BRAFi (BRAF inhibitor)-resistant melanoma cells, leading to DNA cytotoxicity, which caused G2/M phase arrest and apoptosis. Conclusions Taken together, our findings indicate that vitexin compound 1 might be a promising therapeutic Chinese medicine for melanoma treatment regardless of BRAFi resistance.

To investigate the feasibility and effectiveness of high-resolution readout-segmented echo planar imaging (rs-EPI), diffusion-weighted imaging (DWI) is used simultaneously with multi-slice (SMS) imaging (SMS rs-EPI) for the differentiation of breast malignant and benign lesions in comparison to conventional rs-EPI on a 3T MR scanner. A total of 102 patients with 113 breast lesions underwent bilateral breast MRI using a prototype SMS rs-EPI sequence and a conventional rs-EPI sequence. Subjective image quality was assessed using a 5-point Likert scale (1 = poor, 5 = excellent). Signal-to-noise ratio (SNR), lesion contrast-to-noise ratio (CNR) and apparent diffusion coefficients (ADC) value of the lesion were measured for comparison. Receiver operating characteristic curve analysis was performed to evaluate the diagnosis performance of ADC, and the corresponding area under curve (AUC) was calculated. The image quality scores in anatomic distortion, lesion conspicuity, sharpness of anatomical details and overall image quality of SMS rs-EPI were significantly higher than those of conventional rs-EPI. CNR was enhanced in the high-resolution SMS rs-EPI acquisition (6.48 ± 1.71 vs. 4.23 ± 1.49; p < 0.001). The mean ADC value was comparable in SMS rs-EPI and conventional rs-EPI (benign 1.45 × 10−3 vs. 1.43 × 10−3 mm2/s, p = 0.702; malignant 0.91 × 10−3 vs. 0.89 × 10−3 mm2/s, p = 0.076). The AUC was 0.957 in SMS rs-EPI and 0.983 in conventional rs-EPI. SMS rs-EPI technique allows for higher spatial resolution and slight reduction of scan time in comparison to conventional rs-EPI, which has potential for better differentiation between malignant and benign lesions of the breast.

Objective: To explore whether the pretreatment dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and radiomics signatures were associated with pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer. Method: A retrospective review of 70 patients with breast invasive carcinomas proved by biopsy between June 2017 and October 2020 (26 patients were pathological complete response, and 44 patients were non-pathological complete response). Within the pre-contrast and five post-contrast dynamic series, a total of 1037 quantitative imaging features were extracted from in each phase. Additionally, the Δfeatures (the difference between the features before and after the comparison) were used for subsequent analysis. The least absolute shrinkage and selection operator (LASSO) regression method was used to select features related to pCR, and then use these features to train multiple machine learning classifiers to predict the probability of pCR for a given patient. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the predictive performances of the radiomics model for each of the five phases of time points. Result: Among the five phases, each individual phase performed with AUCs ranging from 0.845 to 0.919 in predicting pCR. The best single phases performance was given by the 3rd phase (AUC = 0.919, sensitivity 0.885, specificity 0.864). 5 of the features have significant differences between pCR and non-pCR groups in each phase, most features reach their maximum or minimum in the 2nd or 3rd phase. Conclusion: The radiomic features extracted from each phase of pre-treatment DCE-MRI possess discriminatory power to predict tumor response.

Objectives: To compare the application value of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) in breast galactography. Materials and Methods: A total of 128 patients with pathological nipple discharge (PND) were selected to undergo galactography. DBT and FFDM were performed for each patient after injecting the contrast agent; the radiation dose of DBT and FFDM was calculated, and the image quality was evaluated in consensus by two senior breast radiologists. Histopathologic data were found in 49 of the 128 patients. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for both FFDM- and DBT-galactography were calculated using histopathologic results as a reference standard. Data were presented as percentages along with their 95% confidence intervals (CI). Results: The average age of the 128 patients was 46.53 years. The average glandular dose (AGD) of DBT-galactography was slightly higher than that of FFDM-galactography (p < 0.001). DBT-galactography was 30.7% higher than FFDM-galactography in CC view, while DBT-galactography increased by 21.7% compared with FFDM-galactography in ML view. Regarding catheter anatomic distortion, structure detail, and overall image quality groups, DBT scores were higher than FFDM scores, and the differences were significant for all measures (p < 0.05). In 49 patients with pathological nipple discharge, we found that the DBT-galactography had higher sensitivity, specificity, PPV, and NPV (93.3%, 75%, 97.7%, and 50%, respectively) than FFDM-galactography (91.1%, 50%, 95.3%, and 33.3%, respectively). Conclusions: Compared to FFDM-galactography, within the acceptable radiation dose range, DBT-galactography increases the sensitivity and specificity of lesion detection by improving the image quality, providing more confidence for the diagnosis of clinical ductal lesions.