Search

The expression of hypoxia-inducible factor-1α (HIF-1α) is upregulated in hypoxic environments at the lesions of rheumatoid arthritis (RA), which promoted the polarization of proinflammatory M1 macrophages and inhibited the differentiation of anti-inflammatory M2 to deteriorate synovial inflammation. Since oxygen scarcity at the joints causes an imbalance of macrophages M1 and M2, herein, we designed a cyanobacteria micro-nanodevice that can be spatiotemporally controlled in vivo to continuously producing oxygen in the RA joints for the downregulation of the expression of HIF-1α, thereby reducing the amounts of M1 macrophages and inducing the polarization of M2 macrophages for chemically sensitized RA treatment. The forthputting of temperature-sensitive hydrogel guaranteed the safety of cyanobacteria micro-nanodevice in vivo. Furthermore, the oxygen produced by cyanobacteria micro-nanodevice in a sustained manner enhanced the therapeutic effect of the antirheumatic drug methotrexate (MTX) and discouraged inflammation and bone erosion at RA. This study provided a new approach for the RA treatment of spatiotemporal-controlled release of oxygen in vitro.

Pancreatic cancer (PC) is highly malignant and has a high mortality with a 5-year survival rate of less than 8%. As a member of the roundabout immunoglobulin superfamily of proteins, ROBO1 plays an important role in embryogenesis and organogenesis and also inhibits metastasis in PC. Our study was designed to explore whether ROBO1 has effects on the proliferation of PC and its specific mechanism. The expression of ROBO1 was higher in cancer tissues than in matched adjacent tissues by immunohistochemistry (IHC) and qRT-PCR. Low ROBO1 expression is associated with PC progression and poor prognosis. Overexpression of ROBO1 can inhibit the proliferation of PC cells in vitro, and the S phase fraction can also be induced. Further subcutaneous tumor formation in nude mice showed that ROBO1 overexpression can significantly inhibit tumor growth. YY1 was found to directly bind to the promoter region of ROBO1 to promote transcription by a luciferase reporter gene assay, a chromatin immunoprecipitation (ChIP) and an electrophoretic mobility shift assay (EMSA). Mechanistic studies showed that YY1 can inhibit the development of PC by directly regulating ROBO1 via the CCNA2/CDK2 axis. Taken together, our results suggest that ROBO1 may be involved in the development and progression of PC by regulating cell proliferation and shows that ROBO1 may be a novel and promising therapeutic target for PC.

The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two-layer polydimethylsiloxane (PDMS) configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly. This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities. The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction, serving as the interface between the medium channels and tissue chambers. Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels. Various large-scale microvascular networks were generated and quantified in terms of vessel length and density. Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers. This platform enables the culturing of interconnected, large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications, including basic biological studies and drug screening.

Background Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. Methods We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. Results Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. Conclusions Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.

The foggy environment, particularly in the dense fog, would significantly weaken the general optical imaging capability. In such condition, common optical imaging methods could hardly recognize targets and self-position in an effective manner, severely impacting ship berthing operation. Targeted at ship berthing in foggy days and based on zero background interference of solar-blind ultraviolet (UV) optical electronic signal, calibration and imaging positioning method based on solar-blind UV imagers were studied here, achieving three-dimension positioning with high precision. Direct imaging and accurate positioning for assisting in ship berthing could be realized at the same time. In this article, local positioning effect in the foggy environment was evaluated by applying solar-blind UV imaging band. The measurement results verify that accurate positioning could be achieved in the foggy environment by solar-blind UV anti-fog imaging positioning approach to satisfy demands of ship berthing in foggy days.

Toxic trace elements (TEs), such as Hg, Cr, As, and Pb, emitted from coal-fired industrial boilers (CFIBs) have gained considerable attention because of their harmful effects on environmental quali...

Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing.

BACKGROUND: Disruption of protein folding or inter-subunit interactions in the platelet glycoprotein (GP)Ib-IX complex leads to its abnormally low expression in the plasma membrane, the hallmark of Bernard-Soulier syndrome (BSS). OBJECTIVE: To discover the molecular mechanism by which GPIbα in the absence of GPIbβ and GPIX subunits is targeted for rapid degradation. METHOD: The expression of GPIbα mutants with deletion or replacement of various domains were measured in transiently transfected Chinese hamster ovary (CHO) cells. RESULTS: We report evidence to suggest that induction of the unfolded protein response by the unaccompanied mechanosensory domain (MSD) is a major factor for intracellular degradation and low expression of GPIbα. Removal of the MSD produced the first GPIbα variant that, even in the absence of GPIbβ and GPIX, expressed at a level comparable to that of wild-type GPIbα in the GPIb-IX complex, while retaining its native ligand-binding activity. CONCLUSION: Our finding has important implications on the molecular pathogenesis of BSS and the function of the GPIb-IX complex.

Due to biological safety and negligible toxicity, nitric oxide (NO) therapy has gained increasing interest in the field of cancer therapy during the past few years. However, individual NO cancer therapy normally exhibited limited therapeutic efficiency. In order to acquire satisfactory therapeutic outcomes, the NO therapy is usually combined with other therapeutic treatments, mostly chemotherapy. Herein, we constructed HA-TPP@NORM nanoparticles based on the co-assembly of an NO donor (NORM) and tetraphenylporphyrin (TPP)-modified hyaluronic acid, which can efficiently generate a highly biocidal molecule of peroxynitrite (ONOO−) via the synergistic interactions of the nitric oxide (NO) therapy and photodynamic therapy (PDT) to enhance the cancer therapeutic efficiency. In addition, MTT results exhibited that without light irradiation, the HA-TPP@NORM nanoparticles have favourable biocompatibility with the cell viability above 95% at the maximum TPP concentration (20 μg mL−1). Under simultaneous irradiation with 365 nm and 650 nm light, ONOO− can be efficiently produced in cancer cells via the direct coupling reaction of the generated NO and superoxide anion radical (O2˙−), which significantly enhanced the anticancer effect, when compared with individual NO therapy or PDT therapy. Therefore, the HA-TPP@NORM nanoparticles may provide a new insight into the design of efficiently NO-related cancer therapeutic systems.

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY., Normally, norepinephrine (NE) and acetylcholine (ACh) production is maintained at a balanced level in bone, so that osteocytes cannot generate excessive neuropeptide Y (NPY) to favor bone marrow mesenchymal stem/stromal cell adipogenesis rather than osteogenesis. With aging/estrogen deficiency, sympathetic overactivity, and decreased parasympathetic activity cause NE overproduction and ACh reduction, resulting in excess osteocyte NPY generation and subsequent bone‐fat imbalance.

Engineered Sweat Gland Organoids In article number 2103079, Tao Yue, Lei Dong, Xiaobing Fu, and co‐workers have converted human epidermal keratinocytes into cells with typical properties of sweat gland cells and obtained sweat gland organoids from these cells. Transplanting the organoids into mice successfully restored the vital sweat gland functions during skin wound healing, demonstrating a fast and robust way of personalized sweat gland regeneration in patients with large skin defects. [Image: see text]

Background: Congenital pyriform sinus fistula (CPSF) is a rare branchial cleft deformity. The characteristics and management of CPSF in neonates are different from those in children or adults, and a comprehensive understanding of the imaging features of neonatal CPSF can facilitate its preoperative diagnosis. Thus, the aim of this study was to summarize the ultrasonography (US) and CT imaging findings of CPSF in neonates.Methods: Forty-five full-term neonates with CPSF, confirmed by pathology after surgical resection from January 2012 to October 2020, were included in this retrospective study. All patients underwent preoperative cervical US and contrast-enhanced CT examinations, and the imaging findings were analyzed.Results: Forty-six cervical cystic masses were found in 45 neonates, including one case with bilateral lesions, three cases with lesions on the right side, and 41 cases on the left side. Both US and CT detected neck abnormality among all cases, while the diagnostic accuracy of US (15/46, 32.6%) was lower than that of CT (42/46, 91.3%). Moreover, CT showed significantly higher detection rates of intralesional air bubbles, involvement of the ipsilateral thyroid, deviation of the airway, and expansion into the mediastinal and retropharyngeal space compared with the US. As the age increased, it was more likely to present some features including the absence of air-containing, thick cyst wall, and poorly defined border (ρ Conclusion: CPSF in the neonates showed distinctive imaging findings on contrast-enhanced CT scan, which provides important supplementary information for the diagnosis of CPSF after the initial US examination.

Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin‐A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects., An engineering strategy is shown to generate organoids from reprogrammed human epidermal keratinocytes (HEKs) for the regeneration of human sweat glands (SwGs). The technology enables efficient conversion of HEKs into SwG cell lineages and allows a large‐scale production of tissue‐relevant organoids for personalized SwG regeneration in patients with large skin defects.

The diameter of most blood vessels in cardiovascular and peripheral vascular system is less than 6 mm. Because the inner diameter of such vessels is small, a built-in stent often leads to thrombosis and other problems. It is an important goal to replace it directly with artificial vessels. This paper creatively proposed a preparation method of a small-diameter artificial vascular graft which can form a controllable microstructure on the inner wall and realize a multi-material composite. On the one hand, the inner wall of blood vessels containing direct writing structure is constructed by electrostatic direct writing and micro-imprinting technology to regulate cell behavior and promote endothelialization, on the other hand, the outer wall of blood vessels was prepared by electrospinning PCL to ensure the stability of mechanical properties of composite grafts. By optimizing the key parameters of the graft, a small-diameter artificial blood vessel with controllable microstructure on the inner wall is finally prepared. The corresponding performance characterization experimental results show that it has advantages in structure, mechanical properties, and promoting endothelialization.

Background Trichinella spiralis (T. spiralis) is a parasite occurring worldwide that has been proven to have antitumour ability. However, studies on the antitumour effects of cross antigens between the tumour and T. spiralis or antibodies against cross antigens between tumours and T. spiralis are rare. Methods To study the role of cross antigens between osteosarcoma and T. spiralis, we first screened the cDNA expression library of T. spiralis muscle larvae to obtain the cross antigen gene tumour protein D52 (TPD52), and prepared fusion protein TPD52 and its antiserum. The anti-osteosarcoma effect of the anti-TPD52 antiserum was studied using cell proliferation and cytotoxicity assays as well as in vivo animal models; preliminary data on the mechanism were obtained using western blot and immunohistochemistry analyses. Results Our results indicated that TPD52 was mainly localized in the cytoplasm of MG-63 cells. Anti-TPD52 antiserum inhibited the proliferation of MG-63 cells and the growth of osteosarcoma in a dose-dependent manner. The tumour inhibition rate in the 100 μg treatment group was 61.95%. Enzyme-linked immunosorbent assay showed that injection of anti-TPD52 antiserum increased the serum levels of IFN-γ, TNF-α, and IL-12 in nude mice. Haematoxylin and eosin staining showed that anti-TPD52 antiserum did not cause significant pathological damage. Apoptosis of osteosarcoma cells was induced by anti-TPD52 antiserum in vivo and in vitro. Conclusions Anti-TPD52 antiserum exerts an anti-osteosarcoma effect by inducing apoptosis without causing histopathological damage. Graphical abstract

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation–phenotype association. At this time, CE has evaluated putative mutation–phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

Purpose: To observe the clinical efficacy of conbercept in the treatment of choroidal neovascularization (CNV) secondary to pathologic myopia.Methods: We used retrospective analysis of the clinical data of 20 patients (24 eyes) with pathologic myopia choroidal neovascularization (PM-CNV). All patients were treated with intravitreal injection of conbercept 0.5 mg (0.05 ml), a vascular endothelial growth factor (VEGF) receptor fusion protein, and all patients completed at least 6 months of follow-up. Fundus, best corrected visual acuity (BCVA), fundus fluorescein angiography (FFA), optical coherence tomography (OCT), multifocal electroretinogram (mfERG) were assessed before and after treatment. Primary outcome was the functional change in amplitude by mfERG and secondary outcome was the structural change in central macular thickness (CRT) by OCT. The CNV area, leakage of CNV lesions, ocular and systemic adverse events were observed before and after treatment.Results: The BCVA were 64.33 ± 10.83 letters, 65.42 ± 11.24 letters, 67.67 ± 7.07 letters after treatment 1, 3, 6 month, respectively, which showed improvement compared with the baseline (P < 0.05). The CRT decreased significantly from 308.50 ± 45.48 μm to 219.63 ± 30.27 μm, 221.33 ± 40.65 μm, 220.96 ± 33.09 μm after treatment 1, 3, 6 month, respectively (P < 0.05). The P1 response of mfERG amplitude improved from 40.71 ± 9.69 nv/deg2 to 50.67 ± 9.48 nv/deg2, 54.92 ± 8.45 nv/deg2, 55.67 ± 6.74 nv/deg2 after treatment 1, 3, 6 month, respectively (P < 0.05). After 6 months of treatment, the leakage of CNV lesions disappeared in 20 (83.3%) eyes, and the leakage area of CNV lesions was significantly reduced in 4 (16.7%) eyes.Conclusion: The intravitreal injection of conbercept significantly reduced CRT and the CNV area, inhibited the leakage of CNV, improved the BCVA, increased the response of mfERG amplitude, and restored the retinal function. The intravitreal injection of conbercept can change the morphology and function of the macular in PM-CNV, which is safe and effective for the treatment of PM-CNV.

Background: This study aimed to compare the Hospital Anxiety and Depression Scale (HADS) and the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in evaluating anxiety and depression in psoriatic arthritis (PsA) patients. Methods: A total of 70 PsA patients were enrolled. Demographic and clinical characteristics were collected after enrollment. HADS-A and SAS were used to evaluate the anxiety of PsA patients, while HADS-D and SDS were used to evaluate the depression of PsA patients. Results: Similar results were observed in detecting the rate of anxiety by HADS-A and SAS (27.1 vs. 21.4%, p = 0.424), and there was no difference in classifying the severity of anxiety by HADS-A and SAS (p = 0.347). The Spearman test also disclosed that HADS-A score was positively associated with SAS score (p <0.001). The rates of depression were similar by HADS-D and SDS (27.1 vs. 40.0%; p = 0.108). However, different results were observed in grading the severity of anxiety by HADS-D and SDS (p = 0.009), and no correlation was observed between HADS-D and SDS scores (p = 0.138). The consumption of time for HADS assessment was shorter than that for SAS/SDS assessment (p < 0.001). In addition, a positive correlation of HADS-A score with patients’ global assessment (PGA) (p = 0.022) and fatigue scores (p = 0.028) was discovered, and HADS-D score was positively associated with PGA score (p = 0.019). SAS or SDS score presented less correlation with clinical features of PsA patients, which illuminated that only SAS score was positively associated with duration of psoriasis (p = 0.030). Conclusion: HADS seems to be a better option for anxiety and depression assessment than SAS/SDS in PsA patients.

Herein, we present the successful preparation of a new family of porphyrin-functionalized coordination star polymers through the combination of coordination-driven self-assembly and post-assembly polymerization. Their ordered self-assembly behaviour in water and potential applications in photodynamic therapy have been demonstrated.

The transformation biology of sAML from MDS is still not fully understood. Here, we performed a big cohort of paired sequences including target, whole-exome and single cell sequencing to search AML transformation-related last events. The results showed that fifty-five out of the 64 (85.9%) patients presented presumptive last mutation events involving activated signaling, transcription factors, or tumor suppressors. Most last mutation events (63.6%, 35 cases) emerged at the leukemia transformation point. All five of the remaining nine patients analyzed by paired whole exome sequencing showed transformation-related mutations which are not included in the reference targets. Single-cell sequencing indicated that the activated cell signaling route was related to last gene mutation events which take place prior to phenotypic development. Of note, last gene mutation events defined using target sequencing was limited to a small set of genes (less than ten, in the order: NRAS/KRAS, CEBPA, TP53, FLT3, RUNX1, CBL, PTPN11 and WT1, accounted for 91.0% of the mutations). In conclusion, somatic mutations involving in activated signaling, transcription factors, or tumor suppressors appeared to be a precondition for AML transformation from myelodysplastic syndromes. The transformation-related gene mutations may be considered as new therapy targets.

Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.

Background Circular RNAs (circRNAs) are becoming a unique member of non-coding RNAs (ncRNAs) with emerging evidence of their regulatory roles in various cancers. However, with regards to pancreatic ductal adenocarcinoma (PDAC), circRNAs biological functions remain largely unknown and worth investigation for potential therapeutic innovation. Methods In our previous study, next-generation sequencing was used to identify differentially expressed circRNAs in 3 pairs of PDAC and adjacent normal tissues. Further validation of circRHOBTB3 expression in PDAC tissues and cell lines and gain-and-loss function experiments verified the oncogenic role of circRHOBTB3. The mechanism of circRHOBTB3 regulatory role was validated by pull-down assays, RIP, luciferase reporter assays. The autophagy response of PANC-1 and MiaPaca-2 cells were detected by mCherry-GFP-LC3B labeling and confocal microscopy, transmission electron microscopy and protein levels of LC3B or p62 via Western blot. Results circRHOBTB3 is highly expressed in PDAC cell lines and tissues, which also promotes PDAC autophagy and then progression in vitro and in vivo. Mechanistically, circRHOBTB3 directly binds to miR-600 and subsequently acts as a miRNA-sponge to maintain the expression level of miR-600-targeted gene NACC1, which facilitates the autophagy response of PDAC cells for adaptation of proliferation via Akt/mTOR pathway. Moreover, the RNA-binding protein FUS (FUS) directly binds to pre-RHOBTB3 mRNA to mediate the biogenesis of circRHOBTB3. Clinically, circRHOBTB3, miR-600 and NACC1 expression levels are correlated with the prognosis of PDAC patients and serve as independent risk factors for PDAC patients. Conclusions FUS-mediated circRHOBTB3 functions as a tumor activator to promote PDAC cell proliferation by modulating miR-600/NACC1/Akt/mTOR axis regulated autophagy.

Isolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the same sample. The basis of SCV emergence in vivo is not well understood in Gram-negative bacteria. In this study, we interrogated the causal genetic lesions of SCV growth in three pairs of NCV and SCV co-isolates of Escherichia coli, Citrobacter freundii, and Enterobacter hormaechei. We confirmed SCV emergence was attributed to limited genomic mutations: 4 single nucleotide variants in the E. coli SCV, 5 in C. freundii, and 8 in E. hormaechei. In addition, a 10.2 kb chromosomal segment containing 11 genes was deleted in the E. hormaechei SCV isolate. Each SCV had at least one coding change in a gene associated with bacterial oxidative respiration and another involved in iron capture. Chemical and genetic rescue confirmed defects in heme biosynthesis for E. coli and C. freundii and lipoic acid biosynthesis in E. hormaachei were responsible for the SCV phenotype. Prototrophic growth in all 3 SCV Enterobacteriaceae species was unaffected under anaerobic culture conditions in vitro, illustrating how SCVs may persist in vivo.

Chondrocyte apoptosis is an important factor in the development and progression of osteoarthritis (OA). Cryptotanshinone (CTS) can inhibit chondrocyte apoptosis, but the specific mechanism remains unknown. The aim of the present study was to explore how CTS may affect chondrocyte apoptosis. Reverse transcription‑quantitative PCR and western blotting were used to validate microRNA (miR)‑574‑5p, YY1‑associated factor 2 (YAF2), Bcl‑2 and Bax expression levels. H&E, Safranin O and TUNEL staining assays were used to evaluate the apoptosis of arthritic chondrocytes in vivo. A Cell Counting Kit‑8 assay and flow cytometry were performed to detect cell proliferation and apoptosis of chondrocytes in vitro. The methylation level of the miR‑574‑5p promoter was measured via methylation specific PCR. The degree of chondrocyte apoptosis and the expression levels of YAF2 and Bcl‑2 were decreased in the mice with OA, and were increased in the OA + CTS mice, while the expression levels of miR‑574‑5p and Bax showed opposite changes. Furthermore, the degree of chondrocyte apoptosis and the expression levels of the aforementioned key factors in chondrocytes were consistent with those observed in vivo. The methylation degree of the miR‑574‑5p promoter was increased by the addition of CTS, and was reduced after the addition of a methylation inhibitor, 5‑aza‑CdR, indicating that CTS could regulate the methylation of miR‑574‑5p promoter. The present study suggested that CTS could downregulate the expression of miR‑574‑5p by regulating its methylation, and thus, could improve YAF2 expression and affect chondrocyte apoptosis.

Strong links between hearing and cognitive function have been confirmed by a growing number of cross-sectional and longitudinal studies. Seniors with age-related hearing loss (ARHL) have a significantly higher cognitive impairment incidence than those with normal hearing. The correlation mechanism between ARHL and cognitive decline is not fully elucidated to date. However, auditory intervention for patients with ARHL may reduce the risk of cognitive decline, as early cognitive screening may improve related treatment strategies. Currently, clinical audiology examinations rarely include cognitive screening tests, partly due to the lack of objective quantitative indicators with high sensitivity and specificity. Questionnaires are currently widely used as a cognitive screening tool, but the subject’s performance may be negatively affected by hearing loss. Numerous electroencephalogram (EEG) and magnetic resonance imaging (MRI) studies analyzed brain structure and function changes in patients with ARHL. These objective electrophysiological tools can be employed to reveal the association mechanism between auditory and cognitive functions, which may also find biological markers to be more extensively applied in assessing the progression towards cognitive decline and observing the effects of rehabilitation training for patients with ARHL. In this study, we reviewed clinical manifestations, pathological changes, and causes of ARHL and discussed their cognitive function effects. Specifically, we focused on current cognitive screening tools and assessment methods and analyzed their limitations and potential integration.

Improving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila, a gut probiotic, ameliorates systemic inflammation by tightening the intestinal barrier. In this study, fractured mice intragastrically administrated with A. muciniphila were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muciniphila at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis, and can be stimulated by PDGF-BB. Moreover, A. muciniphila treatment significantly reduced gut permeability and inflammation at the early stage. Dextran sulfate sodium (DSS) was used to disrupt the gut barrier to determine its role in fracture healing and whether A. muciniphila still can stimulate bone fracture healing. As expected, A. muciniphila evidently improved gut barrier, reduced inflammation and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muciniphila reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB+ preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidence for the involvement of type H vessels in fracture healing and suggests the potential of A. muciniphila as a promising strategy for bone healing. This article has an associated First Person interview with the first author of the paper., Summary: Akkermansia muciniphila reduces intestinal permeability and alleviates inflammation, inducing more PDGF-BB+ preosteoclasts and type H vessel formation in callus, thus promoting bone fracture healing.

When applied to immunity, forward genetic studies use meiotic mapping to provide strong statistical evidence that a particular mutation is causative of a particular immune phenotype. Notwithstanding this, co-segregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the selection of authentic causative mutations using a machine learning software tool, Candidate Explorer (CE), which integrates 65 data features into a single numeric score, mathematically convertible to the likelihood of verification of any putative mutation-phenotype association. CE has identified most genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

The cochlear implant (CI) has an effective habilitation modality for hearing-impaired children by promoting sound perception, vocalization, and language ability. However, the major challenge that remained was the lack of assessment standards for pediatric CI users, especially prelingually deaf children, to evaluate hearing rehabilitation effectiveness. In the present study, we conducted an oddball paradigm with stimuli varying in pure-tone, syllable, and tonal sounds. After implantation, we utilized cortical auditory evoked potential (CAEP) and mismatch negativity (MMN) to obtain time-domain analysis; meanwhile, the source localization was investigated to obtain spatial accuracy of the plasticity in the auditory cortex. P1 started to emerge at the third month after implantation, but its peak level was not significant until the sixth month. The temporal lobe was activated between the third and sixth months after implantation. The MMN waveform was basically normal approximately after 12 months. These results suggest that the auditory system goes through a critical period of rapid development between three and six months and enters a maturation period after 12 months. This work indicates that CAEPs are more suitable for assessing the early auditory system reconstruction, while MMN performs better in evaluating the advanced auditory function. Furthermore, source localization has proven to be an efficient tool in exploring auditory cortex plasticity, especially for pediatric CI users.

Sarcopenia is a syndrome characterized by progressive systemic muscle loss and decreased function. The loss of systemic muscle mass and decreased function after stroke can't be explained by brain injury alone, and it is considered to be a kind of secondary sarcopenia, which is called stroke-related sarcopenia. More and more evidence shows that stroke-related sarcopenia can promote the occurrence and development of sarcopenia through a variety of pathogenesis, such as immobilization, impaired feeding, sympathetic activation, inflammation and denervation. Post-stroke disability brings difficulties to the screening and diagnosis of sarcopenia. Simple and easy rehabilitation scores and clinical tests can be used for the determination of body function under specific conditions of stroke, as well as for the screening stroke-related sarcopenia. At present, there is still no particularly effective way to stop its progress,however, the combination of rehabilitation exercise, nutrition supply and drugs may delay or even prevent the development of stroke-related sarcopenia. This article reviews the latest progress in the pathogenesis, screening, evaluation and treatment of stroke-related sarcopenia to provide reference for clinical treatment and rehabilitation of stroke.

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aβ). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aβ levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aβ in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aβ clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Angstrom-scale silver particles (AgAPs) and determined the anti-tumor efficacy of fructose-coated AgAPs (F-AgAPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgAPs and aimed to assess whether F-AgAPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgAPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgAPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgAPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgAPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgAPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgAPs-induced apoptosis. Results: The newly obtained F-AgAPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgAPs were excreted through feces. F-AgAPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgAPs as a powerful selective anticancer agent for osteosarcoma therapy.

Objective: To discuss the function of mixed reality (MR) technology in guiding location of intervertebral foramen microscopic puncture and analyze its feasibility and clinical application value. Methods: Sixty patients with lumbar intervertebral disc who were treated between January 2017 to October 2017 were chosen, and classified into navigation group (30 cases) and traditional control (30 cases) according to random number table. Intervertebral foramen microscopic operation was conducted for both groups. MR technology was applied for the navigation group to guide puncture and establish intervertebral foramen microscopic cannula. Traditional C-arm X-ray apparatus was used for traditional group to establish intervertebral foramen microscopic cannula. Intra-operative puncture times, fluoroscopy times, puncture time and VAS score 1d, 3m and 6m after the operation were recorded and compared. Results: Postoperative waist and leg pain symptoms of both groups were relieved obviously, and straight leg raising test for the diseased limb turned to be negative. Intra-operative puncture times, fluoroscopy times, puncture time and operation time had statistical significance decrease. Conclusion: Mixed reality (MR) can accurately guide the establishment of intervertebral foramen microscopic cannula, solve the bottleneck problem of intervertebral foramen microscopic technology, promote puncture success rate, reduce repeated puncture times, avoid by-injury, shorten puncture time and reduce X-ray radiation quantity of operators and patients, so it deserves to be promoted and applied. doi: https://doi.org/10.12669/pjms.36.3.1683 How to cite this:Guo M, Yue S, Wang J, Cui H. Comparative study on the clinical application of mixed reality technology leading micro-invasive intervertebral foramen puncture location and blind puncture location. Pak J Med Sci. 2020;36(3):559-564. doi: https://doi.org/10.12669/pjms.36.3.1683 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. This study aimed to determine whether EVs from human urine-derived stem cells (USC-EVs) could protect against GC-induced ONFH and focused on the impacts of USC-EVs on angiogenesis and apoptosis to explore the mechanism by which USC-EVs attenuated GC-induced ONFH. The results in vivo showed that the intravenous administration of USC-EVs at the early stage of GC exposure could rescue angiogenesis impairment, reduce apoptosis of trabecular bone and marrow cells, prevent trabecular bone destruction and improve bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reversed the GC-induced suppression of endothelial angiogenesis and activation of apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) proteins were enriched in USC-EVs and essential for the USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 attenuated the protective effects of USC-EVs against GC-induced ONFH. Our study suggests that USC-EVs are a promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1. Statement of Significance This study demonstrates that the intravenous injection of extracellular vesicles from human urine-derived stem cells (USC-EVs) at the early stage of glucocorticoid (GC) exposure efficiently protects the rats from the GC-induced osteonecrosis of the femoral head (ONFH). Moreover, this study identifies that the promotion of angiogenesis and inhibition of apoptosis by transferring pro-angiogenic DMBT1 and anti-apoptotic TIMP1 proteins contribute importantly to the USC-EVs-induced protective effects against GC-induced ONFH. This study suggests the promising prospect of USC-EVs as a new nano-sized agent for protecting against GC-induced ONFH, and the potential of DMBT1 and TIMP1 as the molecular targets for further augmenting the protective function of USC-EVs.

Both Young&rsquo, s modulus and specific membrane capacitance (SMC) are two important physical parameters for characterizing cell status. In this paper, we utilized a thin-neck-micropipette aspiration system to simultaneously quantify Young&rsquo, s modulus and SMC value of six types of cell lines in different progression grades, which include four grades from the lowest metastatic potential G1 to the highest potential G4. We investigated how these two physical properties possess heterogeneities in bladder cancer cells with different grades and what roles they might play in grading bladder cancer. The characterization results of these cells of different cancer grades is linearly correlated with the cancer grades, showing that the Young&rsquo, s modulus is negatively linearly correlated with bladder cancer grades, while SMC shows a positive linear correlation. Furthermore, the combination of these two physical properties on a scatter diagram clearly shows the cell groups with different cancer grades, which means that this combination could be a potential tumor grading marker to identify cancer cells with different metastatic potential.

Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. Herein, we found that intravenous administration of EVs from human urine-derived stem cells (USC-EVs) at the early stage of GC exposure rescues angiogenesis impairment, reduces apoptosis of bone marrow and trabecular bone cells, prevent trabecular bone destruction and improves bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reverse GC-induced suppression of endothelial angiogenesis and activation of cellular apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) are enriched in USC-EVs and essential for USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 in USC-EVs attenuates their protective effects against GC-induced ONFH. Our study suggests that USC-EVs are a novel promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1.

Previous studies have reported a higher incidence of depression and anxiety in psoriasis patients compared to the general population, which has important implications for assessment and treatment. In this study, we determined the frequency of depression and anxiety in Chinese patients with psoriasis and its relationship with disease severity and other demographic variables. The study included 208 Chinese patients with psoriasis vulgaris. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) were used to screen for depression and anxiety. The Psoriasis Area and Severity Index (PASI) was used to assess the severity of psoriasis. Of the 208 patients included in the study, 29 patients (13.9%) were positive for moderate-to-severe depression (PHQ-9 ≥ 10) and 22 patients (10.6%) were positive for anxiety (GAD-7 ≥ 10) symptoms. Both positive stress reactors who perceived stress as an exacerbating factor of psoriasis and moderate-to-severe psoriasis were found to be positive predictors for the presence of moderate-to-severe depression or anxiety symptoms while longer duration and late onset age played a protective role. In the sample of Chinese patients with psoriasis there was a clinically significant prevalence of depression and anxiety. Our study suggests that Chinese psoriasis patients should be screened for psychiatric comorbidities.

A T cell sleeper agent against stress Considerable changes in cellular metabolism occur when T cells transition from a resting to an activated state. One side effect of this process is an increase in reactive oxygen species (ROS). These molecules potentiate T cell receptor (TCR) signaling but can also result in detrimental oxidative stress (see the Perspective by Su and Dutta). Yue et al. describe one mechanism by which T cells can resolve this contradiction. Using mice with a T cell-specific deficiency in Schlafen 2 (SLFN2), they found that this protein binds to and protects transfer RNAs from oxidative stress-induced cleavage by the ribonuclease angiogenin. This process is downstream of ROS generation, which allows activated T cells to maintain protein synthesis despite the ROS that would otherwise inhibit translation. Science , this issue p. eaba4220 ; see also p. 683

Xiao-Gang Chen,1 Fu Hua,2 Shou-Guo Wang,1 Yong-Yi Xu,1 Hai-Tao Yue,1 Jin Sun1 1Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu 223300, People’s Republic of China; 2Department of Gynaecology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu 223300, People’s Republic of China Background: Biosynthesis of leukotriene (LT) by arachidonic acid involves 5-lipoxygenase (5-LO) as an important precursor. Here, we evaluated the role of pseudohypericin (PHP) for its postulated 5-LO inhibitory activity along with a Cys-LT receptor antagonist zafirlukast (ZFL) against inflammatory response and tissue injury in mice. Materials and methods: The spinal injury was induced by two-level laminectomy of T6 and T7 vertebrae. The inflammation was assessed by histology, inflammatory mediators by enzyme-linked immunosorbent assay, apoptosis by Annexin-V, FAS staining, terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL) assay and expression of Bax and Bcl-2 by Western blot. Effect on motor recovery of hind limbs was evaluated for 10days postinjury. Results: The spinal injury resulted in tissue damage, apoptosis, edema, infiltration of neutrophils with increased expression of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). The spinal tissue showed elevated levels of prostaglandin E2 (PGE2), and LTB4 and increased phosphorylation of injured extracellular signal-regulated kinase-1/2 (ERK1/2). The PHP, ZFL and combination decreased inflammation, tissue injury and infiltration of neutrophils. Treatment also decreased the levels of PGE2, phosphorylation of extracellular signal-regulated kinase-1/2 (pERK 1/2), LT, TNF-α and COX-2 with a marked reduction in apoptosis and improved the motor function. Conclusion: The present study confirmed 5-LO antagonist activity of PHP and established its neuroprotective role along with ZFL. Keywords: pseudohypericin, zafirlukast, 5-lipoxygenase, Cys-LT, mice

Industrial boilers are a significant anthropogenic source of air pollutant emissions. In this study, a county-based atmospheric emission inventory of particulate matter (PM), PM10, PM2.5, SO2, NOx, organic carbon (OC) and elemental carbon (EC) from industrial boilers over mainland China in 2017 was developed for the first time, based on county-level activity data from ~61,000 coal-fired industrial boilers (CFIBs), ~44,000 biomass-fired industrial boilers (BFIBs), ~71,000 gas-fired industrial boilers (GFIBs) and ~9300 oil-fired industrial boilers (OFIBs), updated emission factors (EFs) and air pollution control device (APCD) efficiencies. The total national PM, PM2.5, PM10, SO2, NOx, OC and EC emissions from industrial boilers in 2017 were estimated to be 1,240, 347, 761, 1,648, 1,340, 13.1 and 15.8 kilotons (kt), respectively. Intensive air pollutant emissions from industrial boilers of more than 1000 kg/km2 were predominantly in north-eastern, northern and eastern China. CFIBs contributed the most (77.6–94.0 %) to air pollutant emissions because of their high air pollutant EFs and the large amounts of coal consumed. BFIBs were the second-highest contributor to national air pollutant emissions, with the contribution of BFIBs to PM2.5, OC and EC emissions in central and southern China reaching up to 42.1 %, 61.7 % and 45.5 %, respectively. There were seasonal peaks in monthly air pollutant emissions in heating regions. The overall uncertainty realting to the new emission inventory was estimated as −25.9 %–22.7 %. Significant air pollutant emission reductions were obtained from 2017 to 2030, and by 2030 the PM, PM10, PM2.5, SO2 and NOx emissions were forecast to decrease by 40.1–84.0 %, 41.6–84.3 %, 44.5–75.2 %, 44.5–75.2 % and 19.5–46.8 % compared to 2017, respectively, under four proposed scenarios. The results of this study showed that differentiated industrial boiler management measures should be developed according to the actual emission characteristics. This work developed a county-based atmospheric emission inventory of PM, PM10, PM2.5, SO2, NOx, OC and EC from Chinese industrial boilers in 2017 for the first time.

Compared with conventional cameras, spectral imagers provide many more features in the spectral domain. They have been used in various fields such as material identification, remote sensing, precision agriculture, and surveillance. Traditional imaging spectrometers use generally scanning systems. They cannot meet the demands of dynamic scenarios. This limits the practical applications for spectral imaging. Recently, with the rapid development in computational photography theory and semiconductor techniques, spectral video acquisition has become feasible. This paper aims to offer a review of the state-of-the-art spectral imaging technologies, especially those capable of capturing spectral videos. Finally, we evaluate the performances of the existing spectral acquisition systems and discuss the trends for future work.

Increasing evidence suggests that capsaicin may play a role in modulating neuronal function and controlling motor behavior. However, the underlying mechanism is still unclear and the activation of transient receptor potential vanilloid 1 (TRPV1) might be involved in. This study investigated the potential neuroprotective role of capsaicin in a rat model of 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Capsaicin was treated intraperitoneally for the 6-OHDA induced PD rats and the locomotor activity and abnormal involuntary movements were found alleviated. Besides, brain oxidative stress (lipid peroxidation, superoxide dismutase and catalase) was also assessed, and oxidative insults were investigated relieved. Both the expression of tyrosine hydroxylase and TRPV1 were increased in the striatal and substantia nigra areas of 6-OHDA induced rats after the treatment of capsaicin by the semi-quantitative analysis of Western Blot. And the immunostaining of substantia nigra further suggested that capsaicin might protect against dopaminergic neuronal loss. Our results showed that TRPV1 might be a novel therapeutic target for PD.

The KI-impregnated activated carbon (KI-AC) was synthesized to investigate its capacity for elemental mercury (Hg0) removal under the simulated flue gas. The Hg0 removal performance is significantly promoted by KI loading. The effect of reaction temperature and activated carbon porosity on Hg0 removal, and calculation on desorption activation energy of adsorbed mercury species were employed to identify the relationships between the physicochemical characteristics of the KI-AC and Hg0 removal capacity. Raising the reaction temperature weakens the function of physisorption in the process of Hg0 removal. The Brunauer-Emmett-Teller (BET) surface area and desorption activation energy of the adsorbed mercury species analyses indicate that the Hg0 removal occurs through a combination of physisorption and chemisorption, and the chemisorption dominates the reaction. In addition, the influences of flue gas components on Hg0 removal over KI-AC were evaluated, and the adsorption mechanisms were proposed. Oxidation of I− ion by the presence of O2 is the substantial reason that facilitates the Hg0 removal. The Hg0 removal performance is promoted by the generation of SO32−/SO42− and slightly frustrated by the competitive adsorption as well as consumption of I2 molecules. Higher concentration of NO inhibits the generation of HgO products. However, the KI-AC sample remains highly active toward Hg0 removal in the presence of NO because of the reaction with active N-containing groups. Additionally, the affinity capacities between Hg0 and the various groups generated on the KI-AC follow the sequence: N → S-containing groups.

Background: Growth differentiation factor 15 (GDF15) has been shown to be protective for dopaminergic neurons in animal and ex vivo experiments. However, little is known about its effect on the human body. Objective: This study investigated associations between serum GDF15 levels and clinical parameters in patients with Parkinson disease (PD). Methods: Idiopathic PD patients (n = 104) and age-matched controls (n = 88) were enrolled. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay. Univariate and multivariate analyses investigated correlations between GDF15 and clinical characteristics, including disease severity by the Unified PD Rating Scale (UPDRS)-III. The diagnostic value of GDF15 was evaluated by receiver-operating characteristic curve (ROC) analysis. Results: The serum GDF15 levels of the PD patients were significantly higher than those of the healthy controls. In PD patients, serum GDF15 levels in men were significantly higher than in women. GDF15 levels correlated with age, gender, disease duration, and UPDRS-III score. After adjusting for confounding factors, multiple linear regression analysis showed that the serum GDF15 level (β = 0.015, p = 0.001) was an independent risk factor for UPDRS-III score. In ROC analysis, GDF15 achieved an area under the curve of 0.86 for the identification of PD, with a sensitivity of 71.15% and a specificity of 87.50%. Conclusion: GDF15 may be a potential biomarker for the diagnosis and monitoring of motor severity in PD.