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Abstract Background Most Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine blood donor screening for HBV infection since 2015, and a few centers upgraded MP to individual donation (ID) NAT screening recently, raising urgent need for cost-benefit analysis of different screening strategies. In an effort to prevent transfusion-transmitted infections (TTIs) for HBV, cost-benefit analyses of three different screening strategies: HBsAg alone, HBsAg plus MP NAT and HBsAg plus ID NAT were performed in blood donors from southern China where HBV infection was endemic. Methods MP-6 HBV NAT and ID NAT were adopted in parallel to screen blood donors for further comparative analysis. On the basis of screening data and the documented parameters, the number of window period (WP) infection, HBV acute infection, chronic hepatitis B infection (CHB) and occult hepatitis B infection (OBI) was evaluated, and the potential prevented HBV TTIs and benefits of these three strategies were predicted based on cost-benefit analysis by an estimation model. Results Of 132,323 donations, the yield rate for HBsAg-/DNA + screened by ID NAT (0.12%) was significantly higher than that by MP NAT (0.058%, P

Abstract Background Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously. Case presentation We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment. Conclusions This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians’ understanding of this disease for early detection, diagnosis and treatment.

Ovarian steroid cell tumor, not otherwise specified (SCT-NOS), is a rare subtype of sex cord-stromal tumor, characterized by hirsutism and virilization. There are, however, few tumor markers reported in the tumor. The following is a case report. Six years ago, the patient underwent a left adnexectomy after being diagnosed with a yolk sac tumor. Her serum CA72-4 levels were significantly elevated when she was diagnosed with SCT-NOS. She suffered from hirsutism and oligomenorrhea with long menstrual cycles. SCT-NOS was confirmed by her histopathological examination. When the tumor was diagnosed, serum CA72-4 levels were elevated. Following tumor resection, serum CA72-4 levels returned to the average reference interval. Whole-exome sequencing (WES) was utilized to identify ten mutations in MKI67, TICAM1, CHD3, ARID5B, ERBB4, POLD1, FZR1, MTCP1, TBX3, and CLTC genes.

ObjectiveThe cingulate sulcus sign (CSS) has been observed in patients with idiopathic normal pressure hydrocephalus (iNPH), suggesting potential disruptions in cerebrospinal fluid circulation and compromised glymphatic system. Although there are similarities in the underlying mechanisms between cerebral small vessel disease (CSVD) and iNPH, the relationship between CSS and CSVD remains unclear. This study aimed to investigate the prevalence and potential mechanisms of CSS in patients with CSVD.MethodsData from patients diagnosed with CSVD at Shengjing Hospital of China Medical University between January 2020 and October 2022 were retrospectively collected, including general information, global cognitive function [assessed by measuring Mini-Mental State Examination (MMSE)], and four CSVD magnetic resonance imaging (MRI) markers [(white matter hyperintensity (WMH), cerebral microbleeds (CMBs), lacunes, and enlarged perivascular spaces (EPVS)], CSS and the Evan’s index (EI).ResultsA total of 308 patients were included, and CSS was detected in 80 patients (26%). Univariate analysis revealed that MMSE scores in the CSS group were significantly lower compared to the non-CSS group (p < 0.001). Multivariable analysis showed an independent correlation between CSS and the presence of lacunes (odds ratio [OR] 0.358, 95% confidence interval [CI] 0.193–0.663, p = 0.001), presence of lobar dominant CMBs (OR 2.683, 95%CI 1.385–5.195, p = 0.003), periventricular WMH Fazekas score (OR 1.693, 95% CI 1.133–2.529, p = 0.01), and EI (OR 1.276, 95% CI 1.146–1.420, p < 0.001).ConclusionThis preliminary study showed that CSS can be observed in some patients with CSVD. The presence of CSS may represent different mechanisms of CSVD pathogenesis and reflect differences in the degree of cerebrospinal fluid (CSF)/interstitial fluid (ISF) stasis.

Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.

Abstract Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.

Objective To analyze the results of different methods for reactive samples screened by the enzyme linked immunosorbent assay (ELISA) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood donors. Methods From March to April 2020, a total of 8 632 blood samples in Shenzhen were screened for SARS-CoV-2 total antibodies (TAb, including IgG, IgM, IgA) in plasma using ELISA(PC group), the antibody reactivity samples and their follow up plasma samples (FC group), and samples of disease control group(DC group) from January to April 2020 were detected using the following methods: 1) ELISA method for detecting IgG, IgM, and (or without detection) TAb; 2) pseudovirus neutralizing antibody test(pVNT); 3) western blot (WB) of SARS-CoV-2 antibody. The negative control group(NC group) from February to April 2020 performed ELISA and WB testing. Results Among the 34 total antibody positive samples, 2 were positive for pVNT test, and the total antibody, IgG and WB in the initial screening and tracking testing were positive. Thereafter, it was determined to be confirmed positive. The other 2 cases were positive for pVNT test, while the samples with positive WB results were in the follow-up stage. The TAb, IgG, and pVNT results did not conform to the dynamic evolution of antibodies, and cannot be determined as confirmed positive. Conclusion The infection status of antibody reactivity samples screened by SARS-CoV-2 ELISA can be judged by the logic of pVNT, WB and the dynamic change of antibody.

Objective To analyze the SARS-CoV-2 detection results among blood donors in different periods of COVID-19 pandemic control in Shenzhen and assess the antibody levels and infection status of blood donors in different periods, so as to provide reference for subsequent blood testing strategies. Methods A total of 4 768 plasma samples of blood donors were subjected to pooled testing by nucleic acid testing(NAT) with 8 samples per pool. Additionally, these samples were subjected to a 1000-fold dilution, and the detection of SARS-CoV-2 total antibody was performed by enzyme-linked immunosorbent assay (ELISA). The 4 768 plasma samples were collected from blood donors at different time points in Shenzhen, with inquiries made to determine whether donors during the COVID-19 pandemic were in the convalescence. The antibody positive rates in blood screening samples during different periods of the pandemic and samples from individuals in the convalescence of COVID-19 infection were analyzed. Furthermore, the antibody levels were examined for differences based on gender, age, and blood type. Results All 4 768 plasma samples from blood donors were negative by NAT, while 2 342 samples were detected positive by the SARS-CoV-2 total antibody detection, with a positive rate of 49.1%. These samples from four periods (September 30 to October 3, 2022; November 3 to 6, 2022; December 27 to 31, 2022; January 6 to 18, 2023) were subjected to a 1 000-fold dilution for COVID-19 antibody detection, and the positive rates were 21.3%, 15.8%, 65.9%, and 93.9%, respectively. Conclusion The prevalence of COVID-19 antibodies among blood donors in Shenzhen during different periods of the pandemic varied significantly. There was no difference in antibody prevalence among different genders and blood types, while younger individuals exhibited a higher prevalence of antibodies. The risk of COVID-19 transmission through blood transfusion was found to be extremely low.

This paper has investigated the growth of α grain during lamellar decomposition of Ti‐48Al‐7Nb‐2.5V‐1Cr alloy. In the (α + γ) phase region, the α grains have started to grow by consuming the adjacent α grains, accompanied by decomposition of γ lamellae (γL). Since the growth rate of α grains is faster than the decomposition of γL, the growth of the α grains is hindered by the γL, while the hindering effect decreases with the γL decomposition. Once the hindrance of the γL is gone, the α grains will continue to grow and the grain size can even reach the millimetre level. The α grain growth does not show a specific pattern. The growing α grain may also be consumed by the adjacent α grains, resulting in irregular grain morphology.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Summary: Y-box binding protein 2 (YBX2) is an essential modulator of brown adipose tissue activation, yet the regulation on its own expression and the involved mechanism remains largely unknown. Herein, we report the YBX2 protein level, but not mRNA level, is induced in response to acute β-adrenergic signaling. In this context, YBX2 is a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitates YBX2 accumulation in brown adipocytes by decreasing ubiquitination-mediated degradation. Beyond stabilizing PGC1α mRNA, increased YBX2 upon thermogenic activation assists the expression of glycolytic enzymes, promotes glucose utilization and lactate production. Mechanistically, YBX2 modulates translation of glycolytic genes via direct binding to 5′-UTRs of these genes. Together these findings suggest YBX2 is responsive to thermogenic stimuli by phosphorylation modification, and stabilized YBX2 helps to boost glycolysis and thermogenesis in brown adipocytes.

Neurochemicals, crucial for nervous system function, influence vital bodily processes and their fluctuations are linked to neurodegenerative diseases and mental health conditions. Monitoring these compounds is pivotal, yet the intricate nature of the central nervous system poses challenges. Researchers have devised methods, notably electrochemical sensing with micro-nanoscale electrodes, offering high-resolution monitoring despite low concentrations and rapid changes. Implantable sensors enable precise detection in brain tissues with minimal damage, while microdialysis-coupled platforms allow in vivo sampling and subsequent in vitro analysis, addressing the selectivity issues seen in other methods. While lacking temporal resolution, techniques like HPLC and CE complement electrochemical sensing’s selectivity, particularly for structurally similar neurochemicals. This review covers essential neurochemicals and explores miniaturized electrochemical sensors for brain analysis, emphasizing microdialysis integration. It discusses the pros and cons of these techniques, forecasting electrochemical sensing’s future in neuroscience research. Overall, this comprehensive review outlines the evolution, strengths, and potential applications of electrochemical sensing in the study of neurochemicals, offering insights into future advancements in the field.

Objective To investigate the prognosis of blood donors with occult hepatitis B virus infection (OBI) by long-term follow-up and repeated testing of HBsAg and HBV DNA. Methods From January 1, 2010 to December 31, 2020, voluntary blood donors were screened by both serological and viral nucleic acid(NAT) testing, then samples were further confirmed as HBV DNA positive by manual nested-PCR amplification.A total of 306 cases were detected as HBsAg negative /HBV DNA positive, then followed-up for a long time and re-examined of HBsAg and HBV DNA to confirm whether they had infected with OBI.The prognosis of patients with OBI who experienced long-term immunization was determined by repeated testing. Results A total of 306 HBsAg negative/ HBV DNA positive blood donors had been followed up, and 40(13.07%, 40/306) were recalled frequently for re-examination.Among them, 90%(36/40), 57.5%(23/40), 40% (16/40)were anti-HBc + , anti-HBs + and anti-HBe + , respectively, and 50%(20/40), 40%(16/40), 7.5%(3/40) and 2.5% (1/40)were anti-HBs+ / anti-HBc + , anti-HBc + / anti-HBs -, anti-HBc -/ anti-HBs + and anti-HBc -/ anti-HBs -, respectively.Those 40 blood donors were followed-up for 1-13 times, with the duration of 8-108 months (0.6~9 years).1 donor (2.5%) was followed-up less than 1 year, 11 (27.5%)>1 year and ≤3 years, 23 (57.5%) 23(57.5%)>3 years and ≤5 years, and 5 (12.5%) for more than 5 years.After long-term following up and repeated testing, 50%(20/40)of OBI blood donors turned negative for HBV DNA (HBsAg negative / HBV DNA negative), 42.5% (17/40)were confirmed as OBI infection (HBsAg negative / HBV DNA positive), and 7.5%(3/40) were hard to determine (after repeated testing, the results were either positive or negative). Conclusion After long-term following up and repeated screening, we found that none of the OBI patients turned into acute or chronic HBV infection, and most of them maintained OBI.However, OBI blood donors carry very low load of HBV DNA for a long time, which could lead to false negative results of NAT and bring a great challenge to the safety of blood transfusion.

Utilizing interface engineering to construct abundant heterogeneous interfaces is an important means to improve the absorbing performance of microwave absorbers. Here, we have prepared the MXene/MoS2-ReS2 (MMR) composite with rich heterogeneous interfaces composed of two-dimensional Ti3C2Tx MXene and two-dimensional transition metal disulfides through a facile hydrothermal process. The surface of MXene is completely covered by nanosheets of MoS2 and ReS2, forming a hybrid structure. MRR exhibits excellent absorption performance, with its strongest reflection loss reaching −51.15 dB at 2.0 mm when the filling ratio is only 10 wt%. Meanwhile, the effective absorption bandwidth covers the range of 5.5–18 GHz. Compared to MXene/MoS2 composites, MRR with a MoS2-ReS2 heterogeneous interface exhibits stronger polarization loss ability and superior absorption efficiency at the same thickness. This study provides a reference for the design of transition metal disulfides-based absorbing materials.

Objective To evaluate the performance and clinical application of a high-throughput nucleic acid blood screening detection system for SARS-CoV-2, so as to provide basis and technical means for its application in detection of plasma from recovered COVID-19 patients. Methods The SARS-CoV-2 nucleic acid was detected by real-time fluorescence quantitative PCR, and the sensitivity, precision, anti-interference and other parameters were evaluated. Blood donor samples collected during COVID-19 epidemic period were screened using the detection system to evaluate its applicability. Results The detection limits of gene N and ORF 1ab were 3.98 copies/mL and 9.38 copies/mL, respectively. The CV of high and low concentration samples were both less than 5%. Hemoglobin at 500 mg/dL and triglyceride at 3g/dL had little effect on the results. The detection system can effectively prevent carryover, thus avoiding false positive results. The SARS-CoV-2 nucleic acid blood screening was carried out in a total of 39 306 blood samples, and all samples were negative. Conclusion The established method can meet the needs of SARS-CoV-2 nucleic acid screening therefore ensure the safe application of plasma from recovered COVID-19 patients.

Abstract Cancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy. Graphical Abstract

Abstract Molybdenum disulfide (MoS2) has moderate hydrogen adsorption free energy, making it an excellent alternative to replace noble metals as hydrogen evolution reaction (HER) catalysts. The thickness of MoS2 can affect its energy band structure and interface engineering, which are the avenue way to adjust HER performance. In this work, MoS2 films with different thicknesses were directly grown on the glassy carbon (GC) substrate by atomic layer deposition (ALD). The thickness of the MoS2 films can be precisely controlled by regulating the number of ALD cycles. The prepared MoS2/GC was directly used as the HER catalyst without a binder. The experimental results show that MoS2 with 200-ALD cycles (the thickness of 14.9 nm) has the best HER performance. Excessive thickness of MoS2 films not only lead to the aggregation of dense MoS2 nanosheets, resulting in reduction of active sites, but also lead to the increase of electrical resistance, reducing the electron transfer rate. MoS2 grown layer by layer on the substrate by ALD technology also significantly improves the bonding force between MoS2 and the substrate, showing excellent HER stability.

Abstract Background Human T-cell lymphotropic virus (HTLV) remains a major safety concern for blood supplies. Despite many HTLV positive cases being reported in southeastern China, the detection of HTLV has not been prioritized in routine blood screening. Additionally, data on the prevalence of HTLV infection among blood donors is also limited. The objective of this study was to investigate the prevalence of HTLV among blood donors in three Chinese provinces through their representative blood centers, to evaluate the feasibility of chemiluminescence immunoassay (CLIA) for blood screening. Methods From November 2018 to March 2019, blood plasma samples were collected from Hebei, Changsha, and Shenzhen blood centers and were screened for the HTLV-1/2 antibody using a CLIA and enzyme-linked immunosorbent assay (ELISA). This was followed by confirmatory tests using INNO-LIA HTLV I/II. Results A total of 59,929 blood donations were collected and screened for HTLV-1/2. The reactive rate of CLIA and ELISA among donations in the Shenzhen blood center (0.0943%, 27/28,621) was higher than Hebei (0.0248%, 4/16,144), and Changsha (0.0198%, 3/15,164) (p

Here, the authors report large photothermal nonlinearity mediated by anapole states within subwavelength Si nanodisks, offering a mechanism for dynamic tuning of far-field radiation from multipolar modes. Nonlinear scattering is used to demonstrate the potential for far-field optical localization of Si nanostructures.

Polymeric nanoparticles have been widely used as carriers of drugs and bioimaging agents due to their excellent biocompatibility, biodegradability, and structural versatility. The principal application of polymeric nanoparticles in medicine is for cancer therapy, with increased tumor accumulation, precision delivery of anticancer drugs to target sites, higher solubility of pharmaceutical properties and lower systemic toxicity. Recently, the stimuli-responsive polymeric nanoplatforms attracted more and more attention because they can change their physicochemical properties responding to the stimuli conditions, such as low pH, enzyme, redox agents, hypoxia, light, temperature, magnetic field, ultrasound, and so on. Moreover, the unique properties of stimuli-responsive polymeric nanocarriers in target tissues may significantly improve the bioactivity of delivered agents for cancer treatment. This review introduces stimuli-responsive polymeric nanoparticles and their applications in tumor theranostics with the loading of chemical drugs, nucleic drugs and imaging molecules. In addition, we discuss the strategy for designing multifunctional polymeric nanocarriers and provide the perspective for the clinical applications of these stimuli-responsive polymeric nanoplatforms.

Abstract Background To investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with diabetic macular edema (DME) treated monthly with ranibizumab. Methods We retrospectively analyzed the medical records of all patients who received intravitreal ranibizumab (IVR) treatment for DME at the First Affiliated Hospital of Nanchang University between December 2015 and December 2017. Clinicopathological parameters, including NLR, were evaluated to identify predictors of better outcomes of IVR monotherapy. Results Ninety-one treatment-naïve eyes treated with IVR for DME were retrospectively analyzed in this study. Baseline best-corrected visual acuity (BCVA), neutrophils, NLR, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were negatively correlated with the changes in BCVA at 24 weeks compared with the baseline, while baseline central retinal thickness and lymphocytes were positively correlated with the changes in BCVA at 24 weeks compared with the baseline. Multiple linear regression analysis revealed that NLR was independently associated with the mean change of BCVA between baseline and week 24. In addition, patients with NLR 2.27. Conclusion Pretreatment NLR is independently associated with the BCVA in DME patients treated with IVR, and higher pretreatment NLR may contribute to inferior BCVA outcomes.

Plants are frequently confronted by diverse environmental stress, and the membrane lipids remodeling and signaling are essential for modulating the stress responses. Saline–alkaline stress is a major osmotic stress affecting the growth and development of crops. In this study, an integrated transcriptomic and lipidomic analysis was performed, and the metabolic changes of membrane lipid metabolism in maize (Zea mays) roots under saline–alkaline stress were investigated. The results revealed that phospholipids were major membrane lipids in maize roots, and phosphatidylcholine (PC) accounts for approximately 40% of the total lipids. Under 100 mmol NaHCO3 treatment, the level of PC decreased significantly (11–16%) and the parallel transcriptomic analysis showed an increased expression of genes encoding phospholipase A and phospholipase D/non-specific phospholipase C, which suggested an activated PC turnover under saline–alkaline stress. The plastidic galactolipid synthesis was also activated, and an abnormal generation of C34:6 galactolipids in 18:3 plants maize implied a plausible contribution from the prokaryotic pathway, which could be partially supported by the up-regulated expression of three putative plastid-localized phosphatidic acid phosphatase/lipid phosphate phosphatase. A comprehensive gene–metabolite network was constructed, and the regulation of membrane lipid metabolism under saline–alkaline stress in maize was discussed.

Gap-enhanced Raman tags (GERTs) were widely used in cell or biological tissue imaging due to their narrow spectral linewidth, weak photobleaching effect, and low biological matrix interference. Here, we reported a new kind of graphene-wrapped, petal-like, gap-enhanced Raman tags (GP-GERTs). The 4-Nitrobenzenethiol (4-NBT) Raman reporters were embedded in the petal-like nanogap, and graphene was wrapped on the surface of the petal-like, gap-enhanced Raman tags. Finite-difference time-domain (FDTD) simulations and Raman experimental studies jointly reveal the Raman enhancement mechanism of graphene. The SERS enhancement of GP-GERTs is jointly determined by the petal-like “interstitial hotspots” and electron transfer between graphene and 4-NBT molecules, and the total Raman enhancement factor (EF) can reach 1010. Mesoporous silica was grown on the surface of GP-GERTs by tetraethyl orthosilicate hydrolysis to obtain Raman tags of MS-GP-GERTs. Raman tag stability experiments showed that: MS-GP-GERTs not only can maintain the signal stability in aqueous solutions of different pH values (from 3 to 12) and simulated the physiological environment (up to 72 h), but it can also stably enhance the signal of different Raman molecules. These highly stable, high-signal-intensity nanotags show great potential for SERS-based bioimaging and multicolor imaging.

Three-dimensional compound measurement within a volume of interest is of great importance in industrial manufacturing and the biomedical field. However, there is no current method that can simultaneously perform spatial localization and 3D measurement in a non-scanning manner as well as the identification of material in a volume. In this paper, an Autostereoscopic-Raman Spectrometry-based (ARS) three-dimensional measurement system is proposed. The target object in a large depth range is initially positioned by the autostereoscopic 3D measurement method, and then the accurate position information is cross-checked and obtained by combining the spectral signal. Meanwhile, the spectral signal at the precise excitation position guided by the autostereoscopic signal also carries the material composition information. In order to verify the proposed ARS method, an associated measurement system was developed, and experimental studies of detecting various fibers of different depths in multi-layer glass structure were conducted. The spatial locations and dimensional information of multiple different targets can be measured in a volume, and their material can also be identified at the same time. The average error between the calculated position processed by the ARS system and the actual spatial position is within sub-micron levels, and the success rate of spectrum acquisition reaches 98%.

BackgroundType 2 diabetes mellitus (T2DM) known as non-insulin-dependent diabetes mellitus, which is increasingly acknowledged as being associated with an increased risk for a series of cancers. Pancreatic cancer is currently the fourth most common cause of cancer-related mortality, which has been proved to be worsened by internal diabetic condition. However, the underlying molecular mechanisms are less addressed. Furthermore, current knowledge revealed that therapeutic strategy by anti-diabetes for pancreatic cancer under diabetes condition have no satisfactory efficacy, and nor by chemotherapy in our study.MethodsTo clarify these mysteries and widen our knowledge, both obesity-associated and non-obese-associated T2DM mouse models were generated by chemical induction with streptozotocin (STZ) and leptin receptor knockout (db/db) in mice. Then, the process of tumor progression was researched, and the gene expression profiling of pancreatic cancer in mice was performed using RNA-seq.ResultsOur results showed that pancreatic cancer malignancy was increased with notable proliferation and metastatic potential in two diabetic mice model. Totally, 136 and 64 significantly differentially expressed genes (DEGs) were identified in STZ and db/db mice by transcriptomic analysis. The results also suggested that different carcinogenesis-related genes and potential molecular mechanisms contribute to the malignancy of pancreatic cancer in obesity-associated and non-obesity-associated T2DM. In obesity-associated db/db mice, the GO subcategories associated with most of the genes with downregulated expression are involved in the immune response. However, in non-obesity-associated STZ mice, in addition to the immune response category, the enriched subcategories also included angiogenesis and the extracellular matrix. While, two genes respectively encoding MMP-2 and MMP-9 were simultaneously abnormal up-regulated in pancreatic cancer tissue from diabetic mice of both STZ and db/db, that could act as potential therapeutic targets for significantly suppressing the malignant progression. Furthermore, an optimizing therapeutic strategy was further proposed that combining MMP-2/9 inhibitor with gemcitabine significantly enhanced anti-tumor effects on pancreatic cancer under diabetic condition, providing a theoretical basis for clinical applications.ConclusionsGenerally, this study provides a comprehensive insight into diabetes as a risk factor for pancreatic cancer and has the potential to guide the development of enhanced treatment strategies.

NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice. We reversed these changes in db/db mice by administering a peritoneal injection of MitoQ, an antioxidant targeting mtROS. Similar results were observed in human tubular HK-2 cells subjected to high-glucose (HG) conditions and treated with MitoQ. Treating HK-2 cells with MitoQ suppressed the dissociation of TRX from TXNIP and subsequently blocked the interaction between TXNIP and NLRP3, leading to the inhibition of NLRP3 inflammasome activation and IL-1β maturation. The effects of MitoQ were enhanced by pretreatment with TXNIP siRNA and abolished by pretreatment with monosodium urate (MSU) and TRX siRNA in vitro. These results suggest that mitochondrial ROS-TXNIP/NLRP3/IL-1β axis activation is responsible for tubular oxidative injury, which can be ameliorated by MitoQ via the inhibition of mtROS overproduction. Keywords: Diabetic nephropathy, Mitochondria, Reactive oxygen species (ROS), TRX/TXNIP, NLRP3 inflammasome, MitoQ

Based on degradable pH-responsive hydrogel, we report on an enhanced three-dimensional data encryption security technique in which a pH value is used for information manipulation. Featuring three types of states upon the pH value variation, namely, shrinkage, expansion and degradation, the hydrogel renders a limited pH value window as the “key” for information decryption. The pH-dependent shrinkage-to-expansion conversion of the hydrogel leads to a threshold pH value for retrieving the recorded data, whilst the degradability of the hydrogel, which can be tuned by adjusting the composition ratio of PEGDA/AAc, gives rise to a second threshold pH value for irreversibly sabotaging the retrieved data. Pre-doping silver ions in the hydrogel facilitates explicit recording and reading of binary data in forms of three-dimensional silver patterns through photoreduction and scattering, respectively, with a femtosecond laser. By accurately matching the vertical spacing of the encoded silver nanopatterns with the diffraction-limited focal depth of the decryption microscope, we can tune the pH value to encrypt and retrieve information recorded in layers and set a critical pH value to smash encoded information, which proves a highly secured 3D data encoding protocol. This strategy can effectively enrich data encryption techniques, vastly enhancing data security within unattained chemical dimensions.

Mitochondria play a crucial role in tubular injury in diabetic kidney disease (DKD). MitoQ is a mitochondria-targeted antioxidant that exerts protective effects in diabetic mice, but the mechanism underlying these effects is not clear. We demonstrated that mitochondrial abnormalities, such as defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression and mitochondrial fragmentation, occurred in the tubular cells of db/db mice, accompanied by reduced PINK and Parkin expression and increased apoptosis. These changes were partially reversed following an intraperitoneal injection of mitoQ. High glucose (HG) also induces deficient mitophagy, mitochondrial dysfunction and apoptosis in HK-2 cells, changes that were reversed by mitoQ. Moreover, mitoQ restored the expression, activity and translocation of HG-induced NF-E2-related factor 2 (Nrf2) and inhibited the expression of Kelch-like ECH-associated protein (Keap1), as well as the interaction between Nrf2 and Keap1. The reduced PINK and Parkin expression noted in HK-2 cells subjected to HG exposure was partially restored by mitoQ. This effect was abolished by Nrf2 siRNA and augmented by Keap1 siRNA. Transfection with Nrf2 siRNA or PINK siRNA in HK-2 cells exposed to HG conditions partially blocked the effects of mitoQ on mitophagy and tubular damage. These results suggest that mitoQ exerts beneficial effects on tubular injury in DKD via mitophagy and that mitochondrial quality control is mediated by Nrf2/PINK. Keywords: Mitoq, Diabetic kidney disease, Mitophagy, Tubular

Recent advances in the synthesis of multi-functional nanoparticles have opened up tremendous opportunities for the targeted delivery of genes of interest. Cationic solid lipid nanoparticles (SLN) can efficiently bind nucleic acid molecules and transfect genes in vitro. Few reports have combined SLN with therapy using decoy oligodeoxynucleotides (ODN). In the present study, we prepared SLN to encapsulate STAT3 decoy ODN; then, the properties and in vitro behavior of SLN-STAT3 decoy ODN complexes were investigated. SLN-STAT3 decoy ODN complexes were efficiently taken up by human ovarian cancer cells and significantly suppressed cell growth. Blockage of the STAT3 pathway by SLN-STAT3 decoy ODN complexes resulted in an evident induction of cell death, including apoptotic and autophagic death. The mechanism involved the increased expression of cleaved caspase 3, Bax, Beclin-1 and LC3-II and reduced expression of Bcl-2, pro-caspase 3, Survivin, p-Akt and p-mTOR. In addition, SLN-STAT3 decoy ODN complexes inhibited cell invasion by up-regulating E-cadherin expression and down-regulating Snail and MMP-9 expression. These findings confirmed that SLN as STAT3 decoy ODN carriers can induce cell death and inhibit invasion of ovarian cancer cells. We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy.