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Abstract Schizophrenic patients’ brain tumor magnetic resonance imaging (MRI) images are important references for doctors to diagnose and treat schizophrenia. However, automatic segmentation of these images is a professional and tedious task. Existing methods suffer from problems such as large model parameters, long computation time, and inadequate image processing. To achieve more accurate segmentation of brain tumors, we propose brain tumor MRI images for automatic segmentation using self-supervised contrastive learning in schizophrenia patients (BTCSSSP). First, a denoising algorithm based on progressive principal component analysis approximation and adaptive clustering is designed to process the noisy MRI images. Second, a brightness-aware image enhancement algorithm is developed to address the problems of non-uniformity, unclear boundaries, and poor spatial resolution of the MRI images. Finally, a cross-scale U-Net network with selective feature fusion attention module is designed based on self-supervised contrastive learning to achieve automatic segmentation of brain tumor MRI images. The results show that the BTCSSSP method yields higher Recall and Precision than existing methods. The maximum recall is 95%, and the image segmentation precision is 95%, thus indicating good practical applicability.

ABSTRACTRecently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and surface exposure of calreticulin (CALR) in multiple myeloma (MM) cells responding to bortezomib. Hence, GABARAP-defective MM cells fail to undergo immunogenic cell death.

ABSTRACTRecently, we showed that an autologous DC-based vaccine induces an increase in immunosuppressive PD-L1+ tumor-associated macrophages (TAM) both in the tumor and the tumor draining lymph nodes, thereby blunting the efficacy of therapeutic immunization. Only the combination of the DC vaccine with anti-PD-L1 immune checkpoint inhibition, but not the use of antibodies targeting PD-1 alone, was able to set off CD8+ cytotoxic T lymphocyte (CTL)-mediated tumor suppression in mice. In sum, we delineated a PD-L1 checkpoint blockade-based strategy to avoid TAM-induced T cell exhaustion during DC vaccine therapy.

Abstract Cancer immunotherapy, alone or in combination with conventional therapies, has revolutionized the landscape of antineoplastic treatments, with dendritic cells (DC) emerging as key orchestrators of anti-tumor immune responses. Among the distinct DC subsets, conventional type 1 dendritic cells (cDC1) have gained prominence due to their unique ability to cross-present antigens and activate cytotoxic T lymphocytes. This review summarizes the distinctive characteristics of cDC1, their pivotal role in anticancer immunity, and the potential applications of cDC1-based strategies in immunotherapy.

BackgroundBracing is an essential part of scoliosis treatment. The standard of brace treatment for patients with scoliosis today is still very variable in terms of brace quality and outcome. The Gensingen brace is a further developed Chêneau brace derivative with individual design, which can be adapted through computer-aided design. ObjectiveThis study aims to generate a template to obtain a database for prospective multicenter studies study to analyze the results of high-corrective asymmetric Gensingen brace treatment for patients with adolescent idiopathic scoliosis (AIS). MethodsA template for the database was created, which contains the patients' basic data (age, menarcheal status, Risser Sign, curve pattern, and daily brace wearing time), the Cobb angles of curvature, and the cosmetically relevant angles of trunk rotation (ATR). A retrospective review of medical records of patients with AIS, who met the Scoliosis Research Society’s inclusion criteria for brace studies, was performed to test the feasibility of the template. Template items were filled in by the researchers. ResultsOut of 115 patients between 2014 and 2018, the complete data of 33 patients followed up at least 3 months after complete Gensingen brace weaning could be analyzed. The mean age was 12 years, the mean Cobb angle was 33.6°, and the mean Risser value was 0.7 at the beginning of the treatment. The mean improvement in the Cobb angle on in-brace x-ray imaging was –26.1० (80% of in-brace correction). The Cobb angle of the major curvature changed as follows: curve stabilization was achieved in 7 (21.2%) cases, and curve improvement was achieved in 26 (78.8%) cases. None of the patients showed a curve progression. The Cobb angle was significantly reduced in the brace at the end of treatment and at follow-up evaluation (P

Most traditional synthetic dyes and functional reagents used in silk fabrics are not biodegradable and lack green environmental protection. Natural dyes have attracted more and more attention because of their coloring, functionalization effects, and environmental benefits. In this study, natural dyes were extracted from lac and used for coloring and functionalization in silk fabrics without any other harmful dyes. The extraction conditions were studied and analyzed by the univariate method. The optimal extraction process was that the volume ratio of ethanol to water was 60:40 with a solid–liquid ratio of 1:10, and reacting under the neutrality condition for 1 h at 70 °C. Silk fabric can be dyed dark owing to the certain lifting property of lac. After being dyed by Al3+ post-medium, the levels of the washing fastness, light fastness, and friction fastness of silk fabric are all above four with excellent fastness. The results show that the dyed silk fabrics have good UV protection, antioxidation, and antibacterial properties. The UV protection coefficient UPF is 42.68, the antioxidant property is 98.57%, and the antibacterial property can reach more than 80%. Therefore, the dyeing and functionalization of silk fabrics by utilizing naturally lac dyes show broad prospects in terms of the application of green sustainable dyeing and functionalization.

ABSTRACTToll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic – polyuridylic acid). In preclinical models, we show that TL-532 is bioavailable after parenteral injection, has an acceptable toxicological profile, and stimulates the production of multiple chemokines and interleukins that constitute pharmacodynamic markers of its immunostimulatory action. When given at a high dose, TL-532 monotherapy reduced the growth of bladder cancers growing on mice. In addition, in immunodeficient mice lacking formylpeptide receptor-1 (FPR1), TL-532 was able to restore the response of orthotopic subcutaneous fibrosarcoma to immunogenic chemotherapy. Altogether, these findings may encourage further development of TL-532 as an immunotherapeutic anticancer agent.

Although humoral responses elicited by infection or vaccine lost the ability to prevent transmission against Omicron, vaccine-induced antibodies may still contribute to disease attenuation through Fc-mediated effector functions. However, Fc effector function elicited by CoronaVac, as the most widely supplied inactivated vaccine globally, has not been characterized. For the first time, our study depicted Fc-mediated phagocytosis activity induced by CoronaVac, including antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent neutrophil phagocytosis (ADNP) activities, and further compared with that from convalescent individuals and CoronaVac recipients with subsequent breakthrough infections. We showed that 2-dose of CoronaVac effectively induced both ADCP and ADNP, but was substantially lower compared to infection, whereas the booster dose further augmented ADCP and ADNP responses, and remained detectable for 52 weeks. Among CoronaVac recipients, ADCP and ADNP responses also demonstrated cross-reactivity against Omicron subvariants, and breakthrough infection could enhance the phagocytic response. Meanwhile, serum samples from vaccinees, convalescent individuals with wildtype infection, BA.2 and BA.5 breakthrough infection demonstrated differential cross-reactive ADCP and ADNP responses against Omicron subvariants, suggesting the different subvariants of spike antigen exposure might alter the cross-reactivity of Fc effector function. Further, ADCP and ADNP responses were strongly correlated with Spike-specific IgG responses and neutralizing activities, indicating coordinated neutralization activity, ADCP and ADNP responses triggered by CoronaVac. Of note, the ADCP and ADNP responses were more durable and cross-reactive than corresponding Spike-specific IgG titers and neutralizing activities. Our study has important implications for optimal boosting vaccine strategies that may induce potent and broad Fc-mediated phagocytic activities.

ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is a prevalent, life-threatening, emergent infectious disease. Currently, reverse transcription-polymerase chain reaction is the gold standard for diagnosing SFTS virus (SFTSV) infection, which requires sophisticated equipment and professional personnel that are frequently unavailable in most SFTS endemic rural areas. Here, we reported a simple, rapid nucleic acid amplification system that combined the catalytic hairpin assembly (CHA) with a lateral flow immunoassay (LFIA) strip-based detection method for SFTSV detection. The detection of SFTSV RNA could be realized by generation of H1-H2 hybrid duplexes labeled with biotin and digoxin, which subsequently added to the LFIA test strips containing streptavidin conjugated with Alexa Fluor 647 as well as anti-digoxin antibodies. Our CHA-based LFIA assay offered high amplification efficiency and specificity with a detection limit of 1 aM. Crucially, this method enabled stable detection of 500 copies/mL of SFTSV within 30 min using clinical serum samples. Therefore, our CHA-based LFIA approach provided a potential useful tool to facilitate early and precise diagnosis of SFTS patients in poorly resourced SFTS endemic areas. Importance Severe fever with thrombocytopenia syndrome (SFTS) is an emerging and potentially fatal infectious disease prevalent in China. Here we report a simple, rapid nucleic acid amplification system, the catalytic hairpin assembly (CHA) in conjunction with a lateral flow immunoassay (LFIA) strip-based detection method for SFTS virus detection, which demonstrated high amplification efficiency and specificity with limit of detection of 1 aM. Most importantly, we also validate our CHA-based LFIA assay using the clinical serum samples, which was fully compatible with reverse transcription-PCR results. Therefore, our strategy provides a potential useful tool to facilitate early and precise diagnosis of SFTS patients especially in poorly resourced SFTS endemic areas.

Flexible and wearable devices are attracting more and more attention. Herein, we propose a self-powered triboelectric nanogenerator based on the triboelectric effect of fish scales. As the pressure on the nanogenerator increases, the output voltage of the triboelectric nanogenerator increases. The nanogenerator can output a voltage of 7.4 V and a short-circuit current of 0.18 μA under a pressure of 50 N. The triboelectric effect of fish scales was argued to be related to the lamellar structure composed of collagen fiber bundles. The nanogenerator prepared by fish scales can sensitively perceive human activities such as walking, finger tapping, and elbow bending. Moreover, fish scales are a biomass material with good biocompatibility with the body. The fish-scale nanogenerator is a kind of flexible, wearable, and self-powered triboelectric nanogenerator showing great prospects in healthcare and body information monitoring.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses a challenge to determine the optimal updated composition of the coronavirus disease 2019 (COVID-19) vaccine. The present study aimed to investigate the immunogenicity of the Delta monovalent vaccine, the Omicron monovalent vaccine, and the Delta and Omicron BA.1 bivalent vaccine. Three COVID-19 vaccines were designed using the heterologous DNA prime-protein boost strategy, with each vaccine containing either Delta receptor-binding domain (RBD) of the spike protein, Omicron RBD, or both Delta and Omicron antigens. Temporal serum antibody binding titers and neutralizing antibody titers induced by the three vaccines in New Zealand White rabbits were analyzed. To further dissect the vaccine elicited antibodies (mAb) responses at the molecular level, a panel of rabbit monoclonal antibodies (RmAbs) was generated by a high-throughput single B cell sorting and discovery pipeline and further comprehensively characterized. The Omicron monovalent vaccine induced higher antibody binding titers and neutralization activities than the Delta and Omicron bivalent vaccine. Four RmAbs with robust neutralization capacity were isolated from rabbits immunized with the Omicron or Delta monovalent vaccine. Notably, 9E11 isolated from the Omicron monovalent vaccine group neutralized all the Omicron subvariants with an IC50 value ranging from 1.5 to 503.6 ng/mL; thus, this vaccine could serve as a prophylactic and therapeutic intervention. Given the increasing incidence of COVID-19 cases due to the Omicron variant, RBD from the Omicron strain could serve as a candidate immunogen that can induce higher neutralization activities against the SARS-CoV-2 Omicron sublineages.

Background: Chronic hepatitis B virus (HBV) infection is one of the common infectious diseases in the world. HBV covalently closed circular DNA (cccDNA) is the initial template of HBV replication, which can exist in human hepatocytes for a long time and is difficult to be completely removed. It has been shown that HBV RNA can directly respond to the levels and transcriptional activity of cccDNA in hepatocytes and can be used as a surrogate marker of cccDNA transcriptional activity. At present, the detection techniques used for quantitative HBV RNA mainly include reverse transcription quantitative polymerase chain reaction (RT-qPCR) and simultaneous amplification and testing (SAT). Methods: In this study, we verified the performance of the SAT method for detecting HBV RNA and the clinical effectiveness of SAT and RT-qPCR, and compared the correlation and consistency of the two detection methods for HBV RNA detection. Results: The results showed that the limit of detection for HBV RNA by SAT method was 50 copies/mL, with a linear range of 1 × 102-1 × 108 copies/mL. There was no difference in HBV RNA levels detected by the two methods. The correlation and consistency of the results were good, with the coefficient of determination of 0.7787 in HBeAg positive group and 0.8235 in HBeAg negative group. Conclusions: Therefore, this study confirmed that the SAT method and RT-qPCR for detecting HBV RNA have good agreement, which are both reliable methods to detect HBV RNA and can replace each other.

Background Most immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics onerous. The identification of novel small molecule immunotherapeutic agents might overcome such limitations.Method For immunopharmacological screening campaigns, we built an artificial miniature immune system in which dendritic cells (DCs) derived from immature precursors present MHC (major histocompatibility complex) class I-restricted antigen to a T-cell hybridoma that then secretes interleukin-2 (IL-2).Results The screening of three drug libraries relevant to known signaling pathways, FDA (Food and Drug Administration)-approved drugs and neuroendocrine factors yielded two major hits, astemizole and ikarugamycin. Mechanistically, ikarugamycin turned out to act on DCs to inhibit hexokinase 2, hence stimulating their antigen presenting potential. In contrast, astemizole acts as a histamine H1 receptor (H1R1) antagonist to activate T cells in a non-specific, DC-independent fashion. Astemizole induced the production of IL-2 and interferon-γ (IFN-γ) by CD4+ and CD8+ T cells both in vitro and in vivo. Both ikarugamycin and astemizole improved the anticancer activity of the immunogenic chemotherapeutic agent oxaliplatin in a T cell-dependent fashion. Of note, astemizole enhanced the CD8+/Foxp3+ ratio in the tumor immune infiltrate as well as IFN-γ production by local CD8+ T lymphocytes. In patients with cancer, high H1R1 expression correlated with low infiltration by TH1 cells, as well as with signs of T-cell exhaustion. The combination of astemizole and oxaliplatin was able to cure the majority of mice bearing orthotopic non-small cell lung cancers (NSCLC), then inducing a state of protective long-term immune memory. The NSCLC-eradicating effect of astemizole plus oxaliplatin was lost on depletion of either CD4+ or CD8+ T cells, as well as on neutralization of IFN-γ.Conclusions These findings underscore the potential utility of this screening system for the identification of immunostimulatory drugs with anticancer effects.

BackgroundPrimary paratesticular liposarcoma is rarely diagnosed among urinary tumors. In this study, through the retrospective analysis of clinical data and literature review, a case of recurrent paratesticular liposarcoma with lymph node metastasis after radical resection has been reported to explore novel strategies for the diagnosis, treatment and prognosis of this rare disease.Case summaryThe present case involved a patient who was misdiagnosed as a left inguinal hernia for the first time two years ago, but was later diagnosed as mixed liposarcoma by using postoperative pathology. Currently, he is readmitted to the hospital with a recurrence of the left scrotal mass for more than 1 year. Combined with the patient's past medical history, we performed radical resection of the left inguinal and scrotal tumors and lymphadenectomy of left femoral vein. The postoperative pathology indicated that well-differentiated liposarcoma was accompanied by mucinous liposarcoma (about 20%), and lymph node metastasis of left femoral vein both of which occurred at the same time. After the operation, we recommended the patient to receive further radiation therapy, but the patient and his family refused, hence we followed up the patient closely for a long time. During the recent follow-up, the patient reported no complaints of discomfort, and no recurrence of mass in the left scrotum and groin area.ConclusionAfter conducting extensive review of literature, we conclude that radical resection remains the key to treat primary paratesticular liposarcoma, while the significance of the lymph node metastasis is still unclear. The potential effects of postoperative adjuvant therapy depends on the pathological type, and hence close follow-up observation is essential.

To solve grid-scale problems and evaluation indicator selection in landscape ecological risk index (LERI) evaluation, this paper takes the Bailong River Basin in Gansu Province (BLRB) as an example. The LERI evaluation formulae and optimal grid scales were determined by screening landscape indices and area changes in the LERI at different grid scales. The evaluation indices were finally obtained according to the landscape characteristics and the correlation analysis of the landscape index value. Through the statistical analysis of the area of the LERI at the grid scale of 1–6 km, the optimal grid scale was determined to be 5 km. There was little change in land use patterns, with the most significant increases in artificial surfaces at 3.29% and 3.58%, respectively. Cultivated land was the only land use type to decrease by 184.3 km2. The LERI drops with the reduced cultivated land area; the landscape ecological medium risk area and cultivated land keep the same spatial distribution. Due to the limitation of the topography, cultivated land is generally distributed below 2500 m altitude, so 2500 m becomes the turning point in the spatial distribution of the LERI. The medium risk below 2500 m dominates the LERI type. Reduced cultivated land was the leading cause of reduced ecological risk according to an overlay analysis. The study of LERI evaluations provides a theoretical basis for sustainable and ecological environmental protection in the BLRB.

ABSTRACT This study investigated oxidative damage and exocrine dysfunction of fetal pancreas caused by maternal nutritional restriction. Eighteen ewes carrying singleton fetus were randomly divided into control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6), restricted group 1 (RG1, 0.33 MJ ME/BW0.75/d, n = 6), and restricted group 2 (RG2, 0.18 MJ ME/BW0.75/d, n = 6) at d 90 of pregnancy. Maternal undernutrition was imposed from d 90 to 140 of pregnancy. At 140 d of gestation, fetal blood and pancreas tissue were collected to determine fetal pancreatic extracellular matrix, antioxidant capacity, and indicators of exocrine dysfunction. With the decrease of maternal nutrition, the fetal body weight, pancreatic weight, and DNA content were reduced in RG2 compared with CG, and increased and thickened collagen fibers were observed in RG2. Fetuses in RG2 exhibited increased collagen 3 (COL3) and fibronectin (FN) levels relative to CG, and the COL1:COL3 ratio was lower than that of the CG. For RG1, we found increased COL3 compared with CG. Malondialdehyde, serum amylase, and serum lipase in fetal pancreas in RG2 increased, but the total antioxidant capacity (T-AOC) decreased compared with the CG. The impaired ovine fetal pancreas growth, antioxidant imbalance, and pancreatic exocrine dysfunction are induced by maternal undernutrition during late pregnancy.

In this study, graphene quantum dots (GQDs) with a diameter of ~3 nm were successfully synthesized and incorporated into a poly(ethylene terephthalate) (PET) matrix to fabricate PET/GQDs nanocomposites. The impact of GQDs on the crystallization and thermal stability of the PET/GQDs nanocomposites was investigated. It was observed that the addition of only 0.5 wt% GQDs into the nanocomposites resulted in a significant increase in the crystallization temperature (peak temperature) of PET, from 194.3 °C to 206.0 °C during the cooling scan process. This suggested that an optimal concentration of GQDs could function as a nucleating agent and effectively enhance the crystallization temperature of PET. The isothermal crystallization method was employed to analyze the crystallization kinetics of the PET/GQDs nanocomposites, and the data showed that 0.5 wt% GQDs significantly accelerated the crystallization rate. Furthermore, the incorporation of GQDs into the PET matrix imparted photoluminescent properties to the resulting PET/GQDs nanocomposites. The PET crystals with GQDs as crystal nuclei and the crazes caused by defects played a vital role in isolating and suppressing the concentration quenching of GQDs. This effect facilitated the detection of defects in PET.

Perovskite-type CsSnCl3 is an attractive candidate for use as a solid electrolyte in all-solid-state chloride-ion batteries because it exhibits high ionic conductivity. However, perovskite-type CsSnCl3 is metastable at room temperature and easily undergoes a phase transition to a stable phase. Here, we prepared perovskite-type CsSn0.95Mn0.05Cl3, in which the Sn2+ in CsSnCl3 is partly substituted with Mn2+, via a mechanical milling method. Differential scanning calorimetry showed that the perovskite-type CsSn0.95Mn0.05Cl3 is stable to −15 °C. Moreover, it exhibits a high chloride ionic conductivity of 2.0 × 10−4 S cm−1 at 25 °C. We demonstrated the room-temperature operation of an all-solid-state chloride-ion battery with a BiCl3 cathode, an Sn anode, and CsSn0.95Mn0.05Cl3 as the electrolyte. The first discharge capacity of the all-solid-state cell at room temperature was 169 mAh g−1 based on the weight of BiCl3. X-ray diffraction and X-ray photoelectron spectroscopic analyses confirmed that the reaction mechanism of the cell is derived from the redox reaction of BiCl3 and Sn.

Abstract Colorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.

Preclinical experimentation revealed that established cancers treated with the immunogenic cell death (ICD) inducer oxaliplatin are sensitized to immune checkpoint inhibitors targeting PD-1. In contrast, no such sensitizing effect is observed when cisplatin, a non-immunogenic cell death inducer is used. Two randomized phase III clinical trials targeting unresectable gastric and gastro-esophageal junction carcinomas apparently validate this observation. Thus, oxaliplatin-based chemotherapy (together with capecitabine or 5-fluorouracil plus leucovorin) favorably interacted with nivolumab, yielding improved outcome. In contrast, the outcome of cisplatin-based chemotherapy (together with capecitabine or 5-fluorouracil) failed to be improved by concomitant treatment with pembrolizumab. These clinical findings underscore the importance of choosing appropriate ICD-inducing cytotoxicants for the development of chemoimmunotherapeutic regimens. Unfortunately, the FDA and EMA have approved PD-1 blockade in combination with “platinum-based chemotherapy” without specifying the precise nature of the platinum-containing drug. This is a non sequitur. Based on the available clinical data, such approvals should be restricted to the use of oxaliplatin.

Objective: To estimate the incidence of Aicardi-Goutières syndrome (AGS) and potassium sodium-activated channel subfamily T member 1 (KCNT1)-related epilepsy in Denmark and to characterize the patients diagnosed with AGS and KCNT1-related epilepsy. Background: AGS and KCNT1-related epilepsy are 2 distinct rare genetic disorders. Due to the rarity of AGS and KCNT1-related epilepsy, the epidemiology remains unclear. The incidences for these diseases or the carriers with disease-related genetic variants remain unknown. Materials and methods: This is a retrospective, non-interventional, population-based study using aggregate data from the Danish population register and hospital-based patient-level data in Denmark to identify persons with genetically confirmed AGS between January 2010 to December 2020 and KCNT1-related epilepsies between January 2012 to December 2020. Cases of these disorders were identified from in-hospital databases, and pathogenic variants were identified and confirmed by Sanger and/or whole exome (panel-based) sequencing. The incidence of AGS and KCNT1-related epilepsy were estimated in separate statistical analyses. Results: A total of 7 AGS patients were identified. The mean age at AGS diagnosis was 19.4 months (median age 14 months). TREX1 (n

Objective: To analyze the characteristics of foot and ankle deformity with ulceration in patients with spina bifida, to conclude experiences on management with improved Ilizarov method in one stage. Methods: 77 cases suffering foot and ankle deformity with ulceration of spina bifida were included from January 2008 to June 2019, in which 30 male and 47 female, aged 6–46 years with an average age of 22.86 years. There were 10 cases on left, 14 on right and 53 on both. The improved Ilizarov method combined soft tissue surgery, bone osteotomy and Ilizarov technique in one stage, by which the ulcer was dressed aseptically and avoid weight bearing preoperatively, no special treatment, no debridement, no flap coverage and no bacterial culture. Antibiotics were given for 3 days routinely, and the dressing was removed 5 days later. If there was exudation, gauze could be used to wrap continually, if there was no swelling and exudation, no need further more caring. General appearance and radiological image of ulcer and deformity were observed during the period of evaluation and treatment, surgical method and complications, foot & ankle function and overall function were evaluated using AOFAS scoring system and special table designed by authors. Results: 77 cases were followed up for 6–132 months with an average of 50.5 months. Achilles tendon subcutaneous lengthening was performed in 2 cases, posterior tibial tendon and Achilles tendon simultaneous released for 31cases, subtalar joint arthrodesis 25 cases, calcaneus osteotomy 5 cases, triple osteotomy 28 cases, ankle arthrodesis 19 cases, internal rotation osteotomy of tibia was performed in 1 case and 1 case in external rotation osteotomy. There were 67 cases using Ilizarov fixators and 10 cases using Hybrid fixators for immobilization and correction. Stable feet were obtained and ulcers healed simultaneously when all deformities of foot and ankle had been corrected. The healing time of ulcer was average 26.5 days ranging 7–36 days, and there was no infection or delayed healing occurred in any case. Ankle ankylosis in 25 cases, 3 cases of pin tract infection, 2 wires were broken. The AOFAS score significantly increased from 70.5 ± 4.5 preoperative to 81.6 ± 3.9 postoperative; based special table evaluating, Excellent 28 cases, Good 42 cases, Fair7 cases. Conclusion: The patients with foot & ankle deformity and ulceration suffered from spinal bifida can be treated by improved Ilizarov method in one stage, and the results are satisfactory with short treatment period and decreased complications. Translational potential of this article: The characteristics of foot and ankle deformity with ulceration inpatients with spina bifida have been analyzed and the experiences on management with improved Ilizarovmethod in one stage have been summarized in this study, which updated treatment concept of neurogenic deformity with ulceration on foot and ankle joint.

Abstract The integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.

Bismaleimide (BMI) resin-based structural adhesives have excellent heat resistance, with important applications demonstrated in the bonding of high-temperature BMI composites. In this paper, we report an epoxy-modified BMI structural adhesive with excellent properties for bonding BMI-based CFRP. We prepared the BMI adhesive using epoxy-modified BMI as the matrix and PEK-C and core–shell polymers as synergistic tougheners. We found that the epoxy resins improve the process and bonding properties of BMI resin but slightly reduce thermal stability. PEK-C and core–shell polymers synergistically improve the toughness and bonding performances of the modified BMI adhesive system and allow the maintenance of heat resistance. The optimized BMI adhesive exhibits excellent heat resistance, with a high glass transition temperature of 208.6 °C and a high thermal degradation temperature of 425.4 °C. Most importantly, the optimized BMI adhesive exhibits satisfactory intrinsic bonding and thermal stability. It has a high shear strength of 32.0 MPa at room temperature and up to 17.9 MPa at 200 °C. The BMI adhesive-bonded composite joint has a high shear strength of 38.6 and 17.3 MPa at room temperature and 200 °C, respectively, indicating effective bonding and excellent heat resistance.

Abstract Chemotherapy, radiation therapy, as well as targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which altogether confer a robust adjuvanticity to dying cancer cells, as they favor the recruitment and activation of antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) as well as secreted ATP, annexin A1 (ANXA1), type I interferon, and high-mobility group box 1 (HMGB1). Additional hallmarks of ICD encompass the phosphorylation of eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known as eIF2α), the activation of autophagy, and a global arrest in transcription and translation. Here, we outline methodological approaches for measuring ICD markers in vitro and ex vivo for the discovery of next-generation antineoplastic agents, the development of personalized anticancer regimens, and the identification of optimal therapeutic combinations for the clinical management of cancer.

Abstract The carbonophosphate Na3FePO4CO3 was synthesized by the mechanical ball milling method for the first time. The composition of the obtained sample with a higher amount of Fe2+ was Na2.66Fe2+ 0.66Fe3+ 0.34PO4CO3 as confirmed by Mössbauer analysis, owing to the good airtight properties of this method. The obtained samples in an organic electrolyte delivered an initial discharge capacity of 124 mAh/g at room temperature, and a larger discharge capacity of 159 mAh/g (1.66 Na+/mole) at 60 °C. With 17 m NaClO4 aqueous electrolyte, a discharge capacity of 161 mAh/g (1.69 Na+/mole) was delivered because of the high ionic conductivity of the concentrated aqueous electrolyte. During the charge-discharge process, the formation of Fe4+ after charging up to 4.5 V and the return of Fe2+ after discharging down to 1.5 V were detected by ex-situ X-ray absorption near edge structure (XANES) analysis.

Concentrated electrolytes have been attracting increasing attention due to their unique properties. However, despite the concern about their thermal stability, few research has been done on their exothermic behaviors, especially with the coexistence of electrodes. Herein, we report the results of detailed investigation into the thermal properties of LiBF4, LiPF6, LiTFSI, and LiFSI/carbonate concentrated solutions and their thermal behaviors with the coexistence of fully lithiated graphite. Concentrated LiBF4 solutions showed no practical application possibilities because they were unstable on C6Li. Increasing the salt concentration decreased the thermal stability of LiPF6/PC solutions with the coexistence of C6Li. The organic salt dominated the thermal behavior of the solution when mixed with C6Li. A drastic exothermic reaction happened at 210–220 °C when C6Li was mixed with LiFSI solutions, indicating a very high thermal risk of LiFSI carbonate solutions as LIB electrolytes. In contrast, LiTFSI solutions showed much milder reactions with C6Li. On the other hand, because of the different LiF content in SEI, the exothermic onset temperature of the C6Li mixture with the concentrated solution increased in the order of LiFSI > LiTFSI > LiPF6. Comprehensively, concentrated LiTFSI electrolytes should be a good choice for LIB from the standpoint of battery safety.

Summary: Here, we describe a protocol for CRISPR/Cas9-mediated gene knockout in conditionally immortalized immature dendritic cells (DCs), which can be limitlessly expanded before differentiation. This facilitates the genetic screening of DC functions in vitro including assessment of phagocytosis, cytokine production, expression of co-stimulatory or co-inhibitory molecules, and antigen presentation, as well as evaluation of the capacity to elicit anticancer immune responses in vivo. Altogether, these approaches described in this protocol allow investigators to link the genotype of DCs to their phenotype.For complete details on the use and execution of this protocol, please refer to Le Naour et al. (2020).

Background Pharmacological autophagy enhancement constitutes a preclinically validated strategy for preventing or treating most major age-associated diseases. Driven by this consideration, we performed a high-content/high-throughput screen on 65 000 distinct compounds on a robotized fluorescence microscopy platform to identify novel autophagy inducers.Results Here, we report the discovery of picropodophyllin (PPP) as a potent inducer of autophagic flux that acts on-target, as an inhibitor of the tyrosine kinase activity of the insulin-like growth factor-1 receptor (IGF1R). Thus, PPP lost its autophagy-stimulatory activity in cells engineered to lack IGF1R or to express a constitutively active AKT serine/threonine kinase 1 (AKT1) mutant. When administered to cancer-bearing mice, PPP improved the therapeutic efficacy of chemoimmunotherapy with a combination of immunogenic cytotoxicants and programmed cell death 1 (PDCD1, better known as PD-1) blockade. These PPP effects were lost when tumors were rendered PPP-insensitive or autophagy-incompetent. In combination with chemotherapy, PPP enhanced the infiltration of tumors by cytotoxic T lymphocytes, while reducing regulatory T cells. In human triple-negative breast cancer patients, the activating phosphorylation of IGF1R correlated with inhibited autophagy, an unfavorable local immune profile, and poor prognosis.Conclusion Altogether, these results suggest that IGF1R may constitute a novel and druggable therapeutic target for the treatment of cancer in conjunction with chemoimmunotherapies.

Objective: We investigated the clinical value of the Controlling Nutritional Status score in evaluating the prognosis of patients with non-muscle invasive bladder cancer. Methods: We conducted a retrospective analysis of the clinical data of 88 patients with non-muscle invasive bladder cancer who underwent transurethral resection of bladder tumor or partial cystectomy between January 2011 and May 2015 in a single center. The patients were divided into groups base on high (>1) and low (≤1) Controlling Nutritional Status score. Results: Clinical and demographic data of the patient groups were analyzed using the Kaplan-Meier method and log-rank test to generate survival curves. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Among the participants, the male-to-female ratio was 70:18 and median age was 64.5 years (range, 25-84 years). The numbers of patients with Controlling Nutritional Status score of 0, 1, 2, 3, 4, 5, and 6 were 26 (29.55%), 21 (23.86%), 20 (22.73%), 12 (13.64%), 5 (5.68%), 1 (1.14%), and 3 (3.41%), respectively. The 5-year recurrence rate was 29 out of 88 patients (32.95%). The recurrence-free survival of the high-score group was significantly lower than that of the low-score group ( P < 0.001). On univariate analysis, age, smoking history, Controlling Nutritional Status score, depth of tumor invasion, pathological grade, and tumor diameter were related to the prognosis of patients with non-muscle invasive bladder cancer. On multivariate analysis, the Controlling Nutritional Status score (hazard ratio, 4.938; 95% confidence interval, 1.392-17.525; P = 0.013) was an independent factor affecting the recurrence-free survival of patients with non-muscle-invasive bladder cancer. Conclusion: Therefore, the Controlling Nutritional Status score could be a simple, cost-effective, and reliable predictor of prognoses among of patients with non-muscle-invasive bladder cancer.

Certain chemotherapeutic agents can exert their anticancer effect through indirect immune-dependent mechanism. Here, the authors screen a library of tyrosine kinase inhibitors and show that crizotinib is an effective stimulator of immunogenic cell death and can potentiate the efficacy of immune checkpoint blockade.

Salmonella spp. is among the main foodborne pathogens which cause serious foodborne diseases. An isothermal real-time recombinase polymerase amplification (RPA) and lateral flow strip detection (LFS RPA) were used to detect Salmonella spp. targeting the conserved sequence of invasion protein A (invA). The Real-time RPA was performed in a portable florescence scanner at 39°C for 20 min. The LFS RPA was performed in an incubator block at 39°C for 15 min, under the same condition that the amplifications could be inspected by the naked eyes on the LFS within 5 min. The detection limit of Salmonella spp. DNA using real-time RPA was 1.1 × 101 fg, which was the same with real-time PCR but 10 times higher than that of LFS RPA assay. Moreover, the practicality of discovering Salmonella spp. was validated with artificially contaminated lamb, chicken, and broccoli samples. The analyzing time dropped from 60 min to proximately 5–12 min on the basis of the real-time and LFS RPA assays compared with the real-time PCR assay. Real-time and LFS RPA assays’ results were equally reliable. There was no cross-reactivity with other pathogens in both assays. In addition, the assays had good stability. All of these helped to show that the developed RPA assays were simple, rapid, sensitive, credible, and could be a potential point-of-need (PON) test required mere resources.

Limited experimental evidence bridges nutrition and cancer immunosurveillance. Here, we show that ketogenic diet (KD) — or its principal ketone body, 3-hydroxybutyrate (3HB), most specifically in intermittent scheduling — induced T cell–dependent tumor growth retardation of aggressive tumor models. In conditions in which anti–PD-1 alone or in combination with anti–CTLA-4 failed to reduce tumor growth in mice receiving a standard diet, KD, or oral supplementation of 3HB reestablished therapeutic responses. Supplementation of KD with sucrose (which breaks ketogenesis, abolishing 3HB production) or with a pharmacological antagonist of the 3HB receptor GPR109A abolished the antitumor effects. Mechanistically, 3HB prevented the immune checkpoint blockade–linked upregulation of PD-L1 on myeloid cells, while favoring the expansion of CXCR3+ T cells. KD induced compositional changes of the gut microbiota, with distinct species such as Eisenbergiella massiliensis commonly emerging in mice and humans subjected to carbohydrate-low diet interventions and highly correlating with serum concentrations of 3HB. Altogether, these results demonstrate that KD induces a 3HB-mediated antineoplastic effect that relies on T cell–mediated cancer immunosurveillance.

Mutations of the gene coding for calreticulin (CALR) that cause the loss of the C-terminal KDEL motif abolish its retention in the endoplasmic reticulum and cause CALR to be secreted from cells. Specific CALR mutants bearing a novel C-terminus can precipitate the manifestation of myeloproliferative diseases via the autocrine activation of the thrombopoietin receptor. We recently employed the retention using selective hooks (RUSH) technology to monitor CALR trafficking and demonstrated the secretion of C-terminally truncated variants of CALR in vitro and in vivo. Of note, extracellular CALR inhibited the phagocytosis of dying cancer cells by dendritic cells (DC). Via this mechanism, mutant CALR induced immunosuppression, which decreased the efficacy of immunogenic anticancer chemotherapies and PD-1 blockade.

Increased exposure of calreticulin (CALR) on malignant cells is associated with therapy-relevant adaptive immune responses and superior therapeutic outcome in solid tumors and haemato-oncological diseases, because surface-exposed CALR acts as an ‘eat-me’ signal facilitating the phagocytosis of stressed and dying cancer cells by immature dendritic cells, thus favoring antitumor immune responses. On the contrary, mutations of the CALR gene that cause the omission of the C-terminal KDEL endoplasmic reticulum retention motif from CALR protein, resulting in its secretion from cells, act as oncogenic drivers in myeloproliferative neoplasms via the autocrine activation of the thrombopoietin receptor. We recently showed that soluble CALR inhibited the phagocytosis of cancer cells by dendritic cells, thus dampening anticancer immune responses. Furthermore, systemic elevations of soluble CALR that is secreted from tumors or that is artificially supplied by injection of the recombinant protein decreased the efficacy of immunotherapy. Thus, depending on its location, CALR can have immunostimulatory or immunosuppressive functions.

Amid controversial reports that COVID-19 can be treated with a combination of the antimalarial drug hydroxychloroquine (HCQ) and the antibiotic azithromycin (AZI), a clinical trial (ONCOCOVID, NCT04341207) was launched at Gustave Roussy Cancer Campus to investigate the utility of this combination therapy in cancer patients. In this preclinical study, we investigated whether the combination of HCQ+AZI would be compatible with the therapeutic induction of anticancer immune responses. For this, we used doses of HCQ and AZI that affect whole-body physiology (as indicated by a partial blockade in cardiac and hepatic autophagic flux for HCQ and a reduction in body weight for AZI), showing that their combined administration did not interfere with tumor growth control induced by the immunogenic cell death inducer oxaliplatin. Moreover, the HCQ+AZI combination did not affect the capacity of a curative regimen (cisplatin + crizotinib + PD-1 blockade) to eradicate established orthotopic lung cancers in mice. In conclusion, it appears that HCQ+AZI does not interfere with the therapeutic induction of therapeutic anticancer immune responses.

Surface treatment is typically required to improve the bonding performance of carbon-fiber-reinforced composites. Herein, a wet peel ply was prepared using bismaleimide (BMI) resins as a matrix resin. The temperature–heating rate extrapolation method and rheological method were employed to study the reaction characteristics and viscosity-temperature characteristics of the matrix in the BMI wet peel ply. The curing temperatures of the BMI wet peel ply and the BMI prepreg were the same (200 °C), making this wet peel ply suitable for co-curing with the BMI prepreg. After treatment with the wet peel ply, the bonding strength of the BMI composite joint showed a mean shear strength of 35.5 MPa, which was 1.72% higher than that of the sanded composite and 17.5% higher than that of the composite treated with the dry peel ply. In addition, the BMI composite treated with the BMI wet peel ply exhibited good bonding stability with a coefficient of variation of 3.9. After damp-heat aging for 1440 h, the retention rate of shear strength at room-temperature was 82.3%. The relatively loosely woven carrier in the BMI wet peel ply increased the surface roughness of the composite, thus improving the bonding strength.

The thermally conductive structural film adhesive not only carries large loads but also exhibits excellent heat-transfer performance, which has huge application prospects. Herein, a novel epoxy (Ep) thermally conductive structural film adhesive was prepared using polyphenoxy (PHO) as the toughening agent and film former, boron nitride (BN) nanosheets as the thermally conductive filler, and polyester fabric as the carrier. When the amount of PHO in the epoxy matrix was 30 phr and the content of nano-BN was 30 wt.% (Ep/PHO30/nBN30), the adhesive resin system showed good film-forming properties, thermal stability, and thermal conductivity. The glass transition temperature of Ep/PHO30/nBN30 was 215 °C, and the thermal conductivity was 209.5% higher than that of the pure epoxy resin. The Ep/PHO30/nBN30 film adhesive possessed excellent adhesion and peeling properties, and the double-lap shear strength at room temperature reached 36.69 MPa, which was 21.3% higher than that of pure epoxy resin. The double-lap shear strength reached 15.41 MPa at 150 °C, demonstrating excellent high temperature resistance. In addition, the Ep/PHO30/nBN30 film adhesive exhibited excellent heat-aging resistance, humidity, and medium resistance, and the shear strength retention rate after exposure to the complicated environment reached more than 90%. The structural film adhesive prepared showed excellent fatigue resistance in the dynamic load fatigue test, the double-lap shear strength still reached 35.55 MPa after 1,000,000 fatigue cycles, and the strength retention rate was 96.9%, showing excellent durability and fatigue resistance.

Systemic anticancer immunity can be reinstated via the induction of immunogenic cell death (ICD) in malignant cells. Thus, certain classes of cytotoxic compounds, for example, anthracyclines, oxaliplatin and taxanes are endowed with the capacity to act on cancer cells to ignite premortem stress pathways that lead to the surface exposure of calreticulin (CALR) and the cellular release of adenosine triphosphate, annexin A1, high mobility group B1 and type-1 interferons. Altogether, these alterations constitute the hallmarks of ICD. Here we report the design of a discovery pipeline for the identification of novel ICD inducers by means of a phenotypic screening platform. The use of fluorescent biosensors as proxies for the manifestation of ICD hallmarks has enabled the exploration of large collections of chemical compounds by automatized screening routines. Imaging-based assessment and phenotypic selection led to the identification of potential ICD inducers that could be validated further in vitro and in vivo, confirming that bona fide ICD inducers possess the capacity to induce immunological long-term memory and to confer resistance against rechallenge with syngeneic tumors. Machine learning algorithms analyzing the physicochemical properties of ICD inducers can assist in the preselection of compounds with potential ICD-stimulatory properties, further accelerating the screening efforts designed to develop new immunotherapeutic agents.

Crizotinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancers (NSLCL) and lymphomas expressing activating translocations or mutations of oncogenic tyrosine kinases (in particular ALK and ROS1). We recently observed that high-dose (final concentration in vivo: ~10 µM) crizotinib can induce immunogenic cell death (ICD) in cancer cells lacking ALK/ROS1 activation through off-target effects that require the inhibition of several other tyrosine kinases. When combined with cisplatin (which alone does not induce ICD), crizotinib sensitizes NSCLC models to subsequent immunotherapy with PD-1 blockade, allowing to cure more than 90% of established orthotopic cancers. Of note, simultaneous treatment of mice with cisplatin, crizotinib and PD-1 blocking antibodies causes acute hepatotoxicity that can be avoided by a sequential regimen involving initial treatment with cisplatin plus crizotinib, followed by PD-1 blockade one week later. It will be important to translate these results obtained in mice into a clinical trial in NSCLC patients.

A systematic search for anticancer agents that may induce the release of high mobility group box 1 (HMGB1) protein from cells into the extracellular space has led to the identification of several drugs capable of elevating plasma HMGB1 levels in vivo, in mice. Such agents include bona-fide immunogenic cell death inducers such as oxaliplatin, as well as a series of epigenetic modifiers, namely azacitidine, decitabine, and suberoylanilide hydroxamic acid (SAHA).

The original version of this Article contained an error in the spelling of the author Lin Xia, which was incorrectly given as Xia Lin. This has now been corrected in both the PDF and HTML versions of the Article.

Self-synthesized rutile iron oxyfluoride (FeOF) was studied as a cathode material for Na-ion batteries. The highly crystalline FeOF provided an initial discharge capacity of 246 mAh g−1 in a voltage range of 1.0⁻4.0 V, followed by 88% of capacity retention after 20 cycles. This discharge-charge reaction of FeOF between 0.8 and 4.0 V are advanced by the Fe2+/Fe3+ redox reaction. That is, no conversion reaction was involved in the application of FeOF as a cathode material for Na-ion batteries because of the low potential of Na-insertion. In addition, the structure change of FeOF from rutile to cubic during Na ion insertion, which was similar to that in Li-ion batteries. No remarkable HF release was detected even up to 700 °C, indicating a low toxic risk of the FeOF cathode. The thermal properties of sodiated and desodiated FeOF electrodes in the associated electrolyte were investigated by DSC (Differential scanning calorimetry) up to 500 °C. Sodiated FeOF electrodes showed larger exothermic heat generation than desodiated ones, especially at a temperature higher than 380 °C. Finally, the thermal stability of FeOF cathodes in the associated Li- and Na-ion battery electrolytes was quantitatively compared with variations of the electrode/electrolyte ratio.

Rutile FeOF was used as a conversion-type cathode material for Li-ion batteries. In the present study, 0.6Li, 1.4Li, and 2.7Li per mole lithiation reactions were carried out by changing the electrochemical discharge reaction depth. The thermal characteristics of the FeOF cathode were investigated by thermogravimetric mass spectrometric (TG-MS) and differential scanning calorimeter (DSC) systems. No remarkable HF release was detected, even up to 700 °C, which indicated a low toxic risk for the FeOF cathode. Changes in the thermal properties of the FeOF cathode via different conversion reaction depths in the associated electrolyte were studied by changing the cathode/electrolyte ratio in the mixture. LiFeOF was found to exothermically react with the electrolyte at about 210 °C. Similar exothermic reactions were found with charged FeOF cathodes because of the irreversible Li ions. Among the products of the conversion reaction of FeOF, Li2O was found to exothermically react with the electrolyte at about 120 °C, which induced the main thermal risk of the FeOF cathode. It suggests that the oxygen-containing conversion-type cathodes have a higher thermal risk than the oxygen-free ones, but controlling the cathode/electrolyte ratio in cells successfully reduced the thermal risk. Finally, the thermal stability of the FeOF cathode was evaluated in comparison with FeF3 and LiFePO4 cathodes.

Macroporous TiO2 photocatalyst was synthesized by a facile nanocasting method using polystyrene (PS) spherical particles as the hard template. The synthesized photocatalyst was characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), thermogravimetry-differential thermogravimetry (TG-DTG), X-ray diffraction (XRD), and N2-sorption. TEM, SEM, and XRD characterizations confirmed that the macroporous TiO2 photocatalyst is composed of anatase phase. The high specific surface area of 87.85 m2/g can be achieved according to the N2-sorption analysis. Rhodamine B (RhB) was chosen as probe molecule to evaluate the photocatalytic activity of the TiO2 catalysts. Compared with the TiO2 materials synthesized in the absence of PS spherical template, the macroporous TiO2 photocatalyst sintered at 500°C exhibits much higher activity on the degradation of RhB under the UV irradiation, which can be assigned to the well-structured macroporosity. The macroporous TiO2 material presents great potential in the fields of environmental remediation and energy conversion and storage.

Human fetal neural stem cells (hNSCs) are used to treat a variety of neurological disorders involving spinal cord injury (SCI). Although their mechanism of action has been attributed to cell substitution, we examined the possibility that NSCs may have neuroprotective activities. The present article studied the action of hNSCs on protecting neurons and promoting corticospinal tract (CST) axon regeneration after SCI. hNSCs were isolated from the cortical tissue of spontaneously aborted human fetuses. The cells were removed from the NSC culture medium to acquire NSCM, thus excluding the effect of cell substitution. Continuous administration of the NSCM after the SCI resulted in extensive growth of the CST in the cervical region and more than tripled the formation of synaptic contacts between CST collaterals and propriospinal interneurons that project from the cervical level of the spinal cord to the lumbar level. NSCM reduced the number of caspase 3-positive apoptotic profiles at 7 days and protected against loss of the neurons 6 weeks after injury. NSCM promoted locomotor recovery with a five-point improvement on the BBB scale in adult rats. Thus, hNSCs help to set up a contour neural circuit via secretory factors, which may be the mechanism for their action in SCI rats. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation .

Objective. To investigate the expression status of Girdin in glioma and the relationship between Girdin expression and the biological behavior of glioma. Materials and methods. The expression status of Girdin in glioma from 560 cases was evaluated by RT-PCR, Western Blot and immunohistochemistry. The relationship between Girdin expression and clinic-pathological parameters as well as prognosis was also studied. Results. The expression of Girdin in high grade glioma was significantly higher than low grade glioma. After universal analysis, the expression of Girdin protein is closely related to KPS score, extent of resection, Ki67 and WHO grade, but it was not related to sex and age. Finally, extent of resection, Ki67 and WHO grade were indentified to be related to the Girdin protein expression in logistic regression. Interestingly, we found that the expression of Girdin is significantly related to the distant metastasis of glioma. After COX regression analysis, KPS score, Extent of resection, Ki67, WHO grade as well as Girdin were observed to be independent prognostic factors. Conclusions. Girdin is differential expressed in the glioma patients and closely related to the biological behavior of Glioma. Finally, Girdin was found to be a strong predictor for the post-operative prognosis.