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Purpose UVB exposure accelerates skin aging and age-associated pigmentation, but their relationship remains unclear. UVB induces premature senescence and melanin production within melanocytes, along with the upregulation of p53 and cellular tyrosinase (TYR). As a tumor suppressor gene, p53 can keep the genome intact by modulating cell apoptosis and growth arrest during DNA injury. It is also associated with age-associated pigmentation, directly or indirectly regulating pigment-related gene expression. Melatonin effectively regulates tyrosinase activity and resists aging. In this study, we investigated the regulation of p53 on TYR to understand the association between premature senescence and senescence-associated pigmentation and determine the mechanism by which melatonin affects UVB-stimulated melanin production. Methods Primary melanocytes were extracted and identified from the male foreskin. The primary melanocytes were transduced using lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR to knock down TYR expression. The melanin content was determined using the NaOH method, 3,4-Dihydroxy-L-phenylalanine (L-DOPA) was oxidized to dopachrome to determine TYR activity, and Western blotting was performed to detect the level of TYR protein. The primary melanocytes were pretreated with Nutlin-3 or PFT-α to upregulate or downregulate p53 levels or melatonin for 12 h and exposed to UVB irradiation at 80 mJ/cm2. The senescence-associated beta-galactosidase (SA-β-gal) kit was used to analyze premature senescence. The levels of p53, p-p53, and TYR protein were detected by performing the automated capillary electrophoresis Western blotting analysis in melanocytes 72 h after UVB irradiation. Wild-type and TYR(–/–) or TYR(+/–) knockout C57BL/6J mice were used to determine the regulatory role of TYR on melanin synthesis in vivo. Additionally, the effect of melatonin on skin erythema and pigmentation induced by UVB irradiation was analyzed in vivo. Results Primary melanocytes turned deep black after L-DOPA staining, indicating higher TYR protein and mRNA expression. Tyrosinase activity and melanin levels induced by UVB irradiation decreased significantly after the primary melanocytes were infected with pLKD-CMV-EGFP-2A-Puro-U6-TYR (P P TYR(–/–) knockout mice were recognized through white hair, whiskers, and paws, and loss of pigments in the eyes. The tyrosinase activity and melanin levels in the whisker follicles of TYR(–/–) knockout mice also decreased significantly (P

As double membrane-encapsulated nanovesicles (30-150 nm), exosomes (Exos) shuttle between different cells to mediate intercellular communication and transport active cargoes of paracrine factors. The anti-inflammatory and immunomodulatory activities of mesenchymal stem cell (MSC)-derived Exos (MSC-Exos) provide a rationale for novel cell-free therapies for inflammatory bowel disease (IBD). Growing evidence has shown that MSC-Exos can be a potential candidate for treating IBD. In the present review, we summarized the most critical advances in the properties of MSC-Exos, provided the research progress of MSC-Exos in treating IBD, and discussed the molecular mechanisms underlying these effects. Collectively, MSC-Exos had great potential for cell-free therapy in IBD. However, further studies are required to understand the full dimensions of the complex Exo system and how to optimize its effects.

Immune checkpoint inhibitors (ICIs) achieve a milestone in cancer treatment. Despite the great success of ICI, ICI therapy still faces a big challenge due to heterogeneity of tumor, and therapeutic response is complicated by possible immune-related adverse events (irAEs). Therefore, it is critical to assess the systemic immune response elicited by ICI therapy to guide subsequent treatment regimens. Positron emission tomography (PET) molecular imaging is an optimal approach in cancer diagnosis, treatment effect evaluation, follow-up, and prognosis prediction. PET imaging can monitor metabolic changes of immunocytes and specifically identify immuno-biomarkers to reflect systemic immune responses. Here, we briefly review the application of PET molecular imaging to date of systemic immune responses following ICI therapy and the associated rationale.

A broad-spectrum “turn-on” fluorescent sensor for organic amines has been established with a bis-catechol-decorated naphthalene scaffold. It is first synthesized through green chemistry processing with lower solvent consumption.

Alzheimer’s disease (AD) is the most common dementia worldwide. The exact etiology of AD is unclear as yet, and no effective treatments are currently available, making AD a tremendous burden posed on the whole society. As AD is a multifaceted and heterogeneous disease, and most biomarkers are dynamic in the course of AD, a range of biomarkers should be established to evaluate the severity and prognosis. Positron emission tomography (PET) offers a great opportunity to visualize AD from diverse perspectives by using radiolabeled agents involved in various pathophysiological processes; PET imaging technique helps to explore the pathomechanisms of AD comprehensively and find out the most appropriate biomarker in each AD phase, leading to a better evaluation of the disease. In this review, we discuss the application of PET in the course of AD and summarized radiolabeled compounds with favorable imaging characteristics.

The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment.

Environmental context Lvliang, one of the main cities on the Fenwei Plain, is a key atmospheric pollution prevention area in China. Identification of sources of aerosols is essential to improving environmental air quality in this region. The quantitative source apportionment of carbonaceous aerosols performed in this study provides a better understanding of their sources and implications for climate and air-quality management policies in the Fenwei plain. Rationale Organic carbon (OC) and elemental carbon (EC) are major components of fine particulate matter (PM2.5), and they are of concern due to their significant impacts on human health and climate. Methodology PM2.5 samples were collected daily during four consecutive seasons from 2018 to 2019. This paper highlights the seasonal variations, sources and transport characteristics of carbonaceous aerosol in Lvliang, China. Results The OC and EC concentrations exhibited strong seasonal variations, with the highest in winter, mainly due to high pollution caused by winter heating in northern cities, and secondary OC (SOC) contribution. The average OC/EC ratio (1.72) in Lvliang was lower than those in most regions in China, further indicating that this region was greatly affected by primary source emissions. The highest SOC/OC ratio in summer (25.3%) was due to the positive correlation between SOC and temperature. Through the positive matrix factorisation (PMF) model, four sources of carbonaceous aerosols were identified: vehicle emissions (31.26%), coal combustion (30.83%), biomass combustion (24.36%) and dust emissions (13.55%). Potential source contribution function (PSCF) results indicated that in addition to the impact of local emissions, coal emissions from Ningxia and Shaanxi, motor vehicle emissions and biomass from Inner Mongolia and Ningxia and dust from Shaanxi and Henan Provinces were the major contributors to pollution. Discussion These data provide key information for formulating emission reduction policies and improving air quality on the Fenwei Plain and highlights the urgent need for inter-regional prevention and control measures for the cities in Lvliang.

Porous organic polymer (POP) coated on a metal-organic framework (MOF) has the functions and advantages of MOF and POP at the same time and has excellent catalytic ability. In this study, an efficient dual-functional core-shell composite MOF@POP with Lewis acid and Brønsted base sites was synthesized using the impregnation method in which MIL-101(Cr) was the core component and polymelamine formaldehyde (PMF) was the shell component. Most importantly, the obtained MIL-101(Cr)@PMF showed perfect catalytic activity in the deacetalization-Knoevenagel tandem reaction. In addition, it could still maintain ultrahigh physical and chemical stability.

Epithelial-to-mesenchymal transition (EMT) is the process by which epithelial cells transform into mesenchymal cells, which plays a significant role in lung fibrotic disease. Transforming growth factor-β1(TGF-β1) is considered to be the most effective EMT inducer. The purpose of this study was to investigate the effect of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) on TGF-β1-induced EMT and the underlying mechanisms in the human bronchial epithelial cell line BEAS-2B.Human bronchial epithelial BEAS-2B cells were treated with TGF-β1 and TNF-α separately or in combination for 24 h, and qRT-PCR, western blotting, immunofluorescence staining, and migration assays were used to investigate the EMT process. Moreover, to further explore the effect of the NF-κB pathway on the EMT process, inhibitor assays (BAY-117082, NF-κB inhibitor), wound healing assays, and western blotting were performed.The results showed that both cytokines enhanced the transformation of BEAS-2B cells from epithelial to mesenchymal cells. In addition, combined treatment with TNF-α and TGF-β1 further reduced E-cadherin expression, which conversely elevated α-SMA and vimentin mRNA and protein levels. Correspondingly, the migration rate of BEAS-2B cells was also increased. Furthermore, inhibiting the NF-κB signaling pathway blocked the expression of EMT-related markers and NOX4 induced by TGF-β1 and TNF-α, as well as cell migration.Taken together, TNF-α and TGF-β1 cooperatively promoted EMT and cell migration in BEAS-2B cells through the NF-κB/NOX4 signaling pathway.

The role that visual discriminative ability plays among giant pandas in social communication and individual discrimination has received less attention than olfactory and auditory modalities. Here, we used an eye-tracker technology to investigate pupil fixation patterns for eight captive male giant pandas Ailuropoda melanoleuca. We paired images (N = 26) of conspecifics against: 1) sympatric predators (gray wolves, tigers), and non-threatening sympatric species (golden pheasant, golden snub-nosed monkey, takin, red panda), 2) conspecifics with atypical fur coloration (albino, brown), and 3) zookeepers/non-zookeepers wearing either work uniform or plain clothing. For each session, we tracked the panda’s pupil movements and measured pupil first fixation point (FFP), fixation latency, total fixation count (TFC) and duration (TFD) of attention to each image. Overall, pandas exhibited similar attention (FFPs and TFCs) to images of predators and non-threatening sympatric species. Images of golden pheasant, snub-nosed monkey and tiger received less attention (TFD) than images of conspecifics, whereas images of takin and red panda received more attention, suggesting a greater alertness to habitat or food competitors than to potential predators. Pandas’ TFCs were greater for images of black-white conspecifics than for albino or brown phenotypes, implying that familiar color elicited more interest. Pandas reacted differently to images of men vs women. For images of women only, pandas gave more attention (TFC) to familiar combinations (uniformed zookeepers and plain-clothed non-zookeepers), consistent with the familiarity hypothesis. That pandas can use visual perception to discriminate intra-specifically and inter-specifically, including details of human appearance, has applications for panda conservation and captive husbandry.

Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract’s health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis.

Purpose:Adjuvant therapy for small, node-negative HER2-positive breast cancer (HER2+ BC) is controversial. We aimed to identify the subgroup that would benefit most from adjuvant chemotherapy and trastuzumab.Experimental Design:We reviewed records of patients with pT1N0M0 HER2+ BC treated at our institution from January 1, 1998, through October 31, 2009. We compared three groups: A, no adjuvant chemotherapy; B, adjuvant chemotherapy only; and C, adjuvant chemotherapy with trastuzumab. We evaluated disease-free survival (DFS), overall survival (OS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) in each group.Results:We reviewed 587 consecutive patients with a median follow-up of 123.0 months. The 10-year DFS rate was 81.0%, 65.4%, and 97.3% in groups A, B, and C, respectively (P < 0.001). The restricted mean survival time ratio did not differ between groups A and B [ratio = 0.982; 95% confidence interval (CI), 0.930–1.036; P = 0.498). Cox regression showed that adjuvant chemotherapy with trastuzumab was associated with better DFS compared with no adjuvant chemotherapy [hazard ratio (HR), 0.071; 95% CI, 0.025–0.204; P < 0.001). Larger tumor size was associated with short DFS (HR, 2.384; 95% CI, 1.549–3.056; P < 0.001); improvements in DFS, OS, DRFS, and BCSS were observed with adjuvant chemotherapy plus trastuzumab in patients with tumors ≥0.8-cm diameter. Receiving adjuvant chemotherapy with trastuzumab was not associated with improved DFS, OS, or DRFS for tumors Conclusions:Adjuvant chemotherapy plus trastuzumab should be recommended for patients with pT1N0M0 HER2+ BC ≥0.8 cm in diameter; adjuvant therapy may not be necessary for tumors

Supplementary Legend

Supplementary Figure S1. Restricted mean survival time among patients who received no adjuvant chemotherapy (group A) and patients who received adjuvant chemotherapy only (group B), in patients with pT1N0M0 HER2-positive breast cancer.

Supplementary table 1. Restricted mean survival time (RMST) analysis of overall survival in patients with pT1N0M0 HER2-positive breast cancer who received no adjuvant chemotherapy (group A) or adjuvant chemotherapy only (group B).

Supplementary Figure S2. Tumor size cutoff and standardized Wilcoxon statistic for (A) disease-free survival (DFS), (B) overall survival (OS), (C) breast cancer-specific survival (BCSS), and (D) distant recurrence-free survival (DRFS) in patients with pT1N0M0 HER2-positive breast cancer.

Background Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field, and can lead to development of novel therapeutic options. Recent findings A series of biological processes induced by TTFields to exert anti-cancer effects have been identified, and applications of TTFields in oncology have been increasingly reported. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). Conclusions As a novel therapeutic strategies, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields-based combination therapies can improve treatment outcomes.

Osteoarthritis (OA) is a multifactorial disease of the whole joint that has a complex pathogenesis. There is currently no cure for OA. Tofacitinib is a broad JAK inhibitor that can have an anti-inflammatory effect. The objective of this study was to investigate the effect of tofacitinib on the cartilage extracellular matrix in OA and determine whether tofacitinib exerts a protective effect by inhibiting the JAK1/STAT3 signaling pathway and upregulating autophagy in chondrocytes. We established an vitro OA model by exposing SW1353 cells to interleukin-1β (IL-1β) and induced OA in rats using the modified Hulth method. We found that IL-1β promoted the expression of OA-related matrix metalloproteinases (MMP-3 and MMP-13), reduced the expression of collagen II, reduced the expression of beclin1 and LC3-II/I, and promoted the accumulation of p62 in SW1353 cells. Tofacitinib attenuated IL-1β-stimulated changes in MMPs and collagen II and restored chondrocyte autophagy. In IL-1β-stimulated SW1353 cells, the JAK1/STAT3 signaling pathway was activated. Tofacitinib inhibited the IL-1β-stimulated expression of p-JAK1 and p-STAT3 and prevented translocation of p-STAT3 to the nucleus. In the rat model of OA, tofacitinib reduced articular cartilage degeneration by delaying cartilage extracellular matrix degradation and increasing chondrocyte autophagy. Our study demonstrates that chondrocyte autophagy was impaired in experimental models of OA. Tofacitinib reduced the inflammatory response and restored the damaged autophagic flux in OA.

Quantification approaches of positron emission tomography (PET) imaging provide user-independent evaluation of pathophysiological processes in living brains, which have been strongly recommended in clinical diagnosis of neurological disorders. Most PET quantification approaches depend on spatial normalization of PET images to brain template; however, the spatial normalization and quantification approaches have not been comprehensively reviewed. In this review, we introduced and compared PET template-based and magnetic resonance imaging (MRI)-aided spatial normalization approaches. Tracer-specific and age-specific PET brain templates were surveyed between 1999 and 2021 for

Ionizing radiation (IR) can induce autophagy and premature senescence; however, the link between them has not been clarified. Our research has shown that X-ray irradiation induces premature senescence in lung adenocarcinoma cells, and its occurrence partially depends on the signal transducer and activator of transcription 3 (STAT3). STAT3 can bind to the promoter region of Beclin1 and regulate its expression. Therefore, it is speculated that there may be a close link between premature senescence and autophagy induced by ionizing radiation in lung adenocarcinoma cells. p62 plays a regulatory role in both autophagy and premature senescence, and it is also an irreplaceable molecule that causes the senescence -associated secretory phenotype (SASP) and a substrate for selective autophagy. This study focused on STAT3, Beclin1 and p62 to clarify the regulatory relationship between IR-induced autophagy and premature senescence.After exposure to 4 Gy X-rays, a β-galactosidase staining kit was used to detect the positive rate of premature senescence. STAT3 was overexpressed by pcDNA3.0-STAT3 transfection, and was inhibited by AG490 and rapamycin. Lung adenocarcinoma cells were transduced with the adenovirus vector GV119-Beclin1 to knockdown the expression of Beclin1, or treated with ATM and ATR inhibitors to inhibit premature senescence. Western blotting was used to examine alterations in the radiation response proteins STAT3 and p-STAT3, senescence-related proteins p62 and GATA4, autophagy-related proteins Beclin1, and LC3-II/LC3-I. The mRNA expression levels of SASP factors, including IL-6 and IL-8, were examined by real-time polymerase chain reaction.The activity of SA-β-gal increased significantly (Radiation induces premature senescence and autophagy in lung adenocarcinoma cells. Autophagy regulates X-ray radiation-induced premature senescence through the STAT3-Beclin1-p62 pathway in lung adenocarcinoma cells.

The delivery of therapeutic cancer agents via nanomaterials has received significant attention. However, because of the absence of tumour targeting, tumour treatment strategies are still not satisfactory. Umbilical cord mesenchymal stem cells are inherently prone to migrate to malignant sites, enabling them to deliver antitumour drugs effectively. Therefore, it is expected to be a promising tool for tumour targeting. In this study, we constructed magnetic drug-loaded nanoparticles comprised of ferroferric oxide and doxorubicin, which were ingested by umbilical cord mesenchymal stem cells and precisely delivered to the tumour sites. Here, we physicochemically characterized the nanoparticles for the particle size, biocompatibility and cellular uptake. The umbilical cord mesenchymal stem cells migration and homing ability before and after drug loading were evaluated. The anti-cancer effect of stem cells loaded with nanoparticles was determined using MCF-7 cells. In vitro studies, the magnetic drug-loaded nanoparticles complex on tumour cells revealed that umbilical cord mesenchymal stem cells could transport magnetic drug-loaded nanoparticles to induce robust apoptosis.

Purpose The number of international students in China has been increasing over the recent decades. The rapid expansion of the international student population aroused concerns over the capacity of Chinese universities to fulfill international students’ expectations toward academic development. Perceiving student learning experiences as an important indicator of higher education quality, this article focuses on undergraduate international students in China and discusses their learning experiences from three perspectives, i.e., perceived learning environment, academic engagement, and student development. Design/Approach/Methods Data were generated by a survey involving 1,428 international students studying for an undergraduate degree at 34 universities in China. Descriptive statistics were calculated, and the structural equation model was applied. Findings The research showed the respondents’ academic development in a range of skills and abilities, while their learning experiences at the Chinese higher education institutions (HEIs) were largely unsatisfactory. Specifically, the research revealed the respondents’ moderate-to-low-level evaluation of perceived classroom learning environment, their low level of academic engagement, and the significant negative influences of the perceived classroom learning environment and academic engagement on their academic development. Originality/Value The analysis holds implications for the enhancement of positive learning experiences of international undergraduate students in China and the improvement of the quality of Chinese international student education. Student learning experiences are an important indicator of the quality of college teaching. Drawing on the data generated by a survey involving 1,428 international students studying for an undergraduate degree at 34 universities in China, this presentation explores the characteristics of international undergraduate students’ learning experiences in Chinese universities and analyzes the relationship among the three dimensions of their learning experiences.

The COVID-19 pandemic presents unprecedented challenges to the management, teaching, and learning in Chinese international education. This special issue focuses on national policies on international student education, institutional risk-management strategies, quality assurance practices, online teaching pedagogy, international student engagement, and factors affecting their satisfaction. We hope that the discussions in this special issue will allow us to share the lessons that we have learned during this crisis, promote international cooperation to cope with common challenges, and support the sustainable development and transformation of international education in China and worldwide in the post-COVID era.

With the impact of the COVID-19 pandemic, Chinese teaching for international students in Chinese universities has largely moved online. Despite the comprehensive literature regarding the influences of environmental factors on domestic students’ learning in traditional learning environment, few studies have addressed the influences of online learning environment (OLE) on international students’ Chinese learning experiences. We focus on international students in intensive Chinese courses at a Chinese university, and explores the influences of OLE on these students’ intrinsic motivation (IM) towards and engagement in Chinese learning during the COVID-19 pandemic. Data were collected from an online questionnaire survey and follow-up interviews. The results revealed that the participants had positive perceptions of the online Chinese learning environment, and that the participants had high levels of IM towards and engagement in their Chinese learning. The results showed the positive impact of the participants’ perceived OLE on their IM and engagement in Chinese learning.

As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (

Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we show that Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) are isolated and identified from edible Portulaca oleracea L with desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4mV). Moreover, we find that oral administration of PELNs can suppress the expressions of pro-inflammation cytokines (TNF-α, IL-6, IL-12, and IL-1β), and increase the levels of anti-inflammatory cytokine (IL-10) in dextran sulphate sodium (DSS)-induced mice and PHLPP2−/− mice spontaneous colitis contributing to alleviate colitis. Furthermore, orally administered PELNs can display great stability in gastrointestinal tract environment, and specifically targeted to desired inflammatory site in mice colitis. In addition, oral administration of PELNs can effectively maintain the diversity and balance of gut microbiota, and specifically induce the differentiation of double-positive CD4+CD8+T cells (DP CD4+CD8+T cells). In summary, our findings suggest that orally administered PELNs brings a novel and natural colon-targeted agent, and open a new therapeutic avenue in the management of UC.