Reaction mechanism and detecting properties of a novel molecularly imprinted electrochemical sensor for microcystin based on three-dimensional AuNPs@MWCNTs/GQDs.

Microcystins with leucine arginine (MC-LR) is a virulent hepatotoxin, which is commonly present in polluted water with its demethylated derivatives [Dha7] MC-LR. This study reported a low-cost molecularly imprinted polymer network-based electrochemical sensor for detecting MC-LR. The sensor was based on a three-dimensional conductive network composed of multi-walled carbon nanotubes (MWCNTs), graphene quantum dots (GQDs), and gold nanoparticles (AuNPs). The molecularly imprinted polymer was engineered by quantum chemical computation utilizing p-aminothiophenol (p-ATP) and methacrylic acid (MAA) as dual functional monomers and L-arginine as a segment template. The electrochemical reaction mechanism of MC-LR on the sensor was studied for the first time, which is an irreversible electrochemical oxidation reaction involving an electron and two protons, and is controlled by a mixed adsorption-diffusion mechanism. The sensor exhibited a great detection response to MC-LR in the linear range of 0.08-2 µg/L, and the limit of detection (LOD) is 0.0027 µg/L (S/N = 3). In addition, the recoveries of the total amount of MC-LR and [Dha7] MC-LR in the actual sample by the obtained sensor were in the range from 91.4 to 116.7%, which indicated its great potential for environmental detection.

Combination of PD-1 inhibitor with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) versus GVD regimen as second-line therapy for relapsed/refractory classical Hodgkin lymphoma.

Patients with classical Hodgkin lymphoma (cHL) who do not achieve complete remission (CR) after second-line chemotherapy have poor clinical outcomes. Besides, conventional salvage chemotherapy regimens have an unsatisfactory CR rate. The present retrospective study reports the efficacy and toxicity of the GVD (gemcitabine, vinorelbine, liposomal doxorubicin) regimen with or without programmed cell death 1 (PD-1) inhibitor for patients with cHL who failed first-line treatment. A total of 103 patients with cHL (GVD+PD-1 group, n = 27; GVD group, n = 76) with response assessment based on positron emission tomography were included. The GVD+PD-1 group tended to have a higher CR rate than GVD group (85·2% vs. 65·8%, P = 0·057) and had a better event-free survival (EFS) (P = 0·034). Subgroup analysis showed that patients with low-risk second-line International Prognostic Score might benefit from the addition of PD-1 inhibitor (GVD+PD-1 vs. GVD, 100·0% vs. 64·7%, P = 0·028) and had better EFS than GVD alone (P = 0·016). Further analysis demonstrated that PD-1 consolidation therapy might provide an EFS benefit (P = 0·007). The toxicity of the GVD+PD-1 regimen was comparable to the GVD regimen, except for higher rates of hypothyroidism and autoimmune pneumonitis, which were manageable. In conclusion, combining a PD-1 inhibitor with a GVD regimen could be a potentially effective second-line therapy for patients with cHL.

Simultaneous quantitative analysis of seven steroid hormones in human saliva: A novel method based on O-ethylhydroxylamine hydrochloride as derivatization reagent.

RATIONALE: Saliva has been widely accepted as a more convenient alternative to serum or plasma in the field of clinical diagnosis. However, the detection of trace components in saliva has been a bottleneck problem. The aim of this work was to develop a highly sensitive and reliable method for simultaneously determining the trace steroid hormones including some with poor ionization efficiency in human saliva by liquid chromatography/tandem mass spectrometry (LC/MS). METHODS: Saliva was deproteinated by acetonitrile containing mixed isotope internal standards and extracted with methyl tert-butyl ether. The extraction solution was dried under a stream of nitrogen and the residue was derivatized using 50 mM O-ethylhydroxylamine hydrochloride in 80% methanol/water solution (v/v). The processed sample was determined by LC/MS in multiple reaction monitoring (MRM) mode. RESULTS: The method was successfully established for the simultaneous quantification of seven steroid hormones in human saliva and showed excellent specificity and sensitivity. The limits of quantification (LOQs) of all steroid hormones were below 5 pg/mL, in particular, the LOQ of progesterone was as low as 0.15 pg/mL. The linear correlation coefficients (r) were greater than 0.9990 in the range of 2-200 pg/mL for T, DHEA, A4, P4, P5, and 17OHP4 and in the range of 5-500 pg/mL for 17OHP5. The intra-day and inter-day variability ranged from 1.86% to 7.83% and 1.95% to 10.4%, respectively. The recovery of the method ranged from 86.9% to 111.1% for all steroid hormones using three spiked concentrations. CONCLUSIONS: A novel LC/MS/MS method was developed for the simultaneous quantification of seven kinds of trace steroid hormones in human saliva. The results of the methodological study showed that the method exhibited excellent sensitivity and reliability for the evaluation of free steroid hormones in the human body. It is believed that this method could provide useful information of steroid hormone metabolism for auxiliary diagnosis of some endocrine disorders.

Waste Cooking Oil-Modified Epoxy Asphalt Rubber Binders with Improved Compatibility and Extended Allowable Construction Time.

The application of crumb rubber from end-of-life tires and waste cooking oil (WCO) in road pavements is of significant importance from an economic and environmental viewpoint. However, the incorporation of crumb rubber greatly shortens the allowable construction time of epoxy asphalt binders due to the high viscosity of the epoxy asphalt rubber (EAR) binder and poor compatibility between crumb rubber and asphalt binder. To lower the viscosity of asphalt rubber, extend the allowable construction time and improve the compatibility of EAR binder, waste cooking oil (WCO) was introduced. The effect of WCO on the viscosity-time behavior, thermal stability, dynamic modulus, glass transitions, crosslink density, damping ability, compatibility, mechanical properties and phase separation of WCO-modified EAR binders was investigated by using the Brookfield viscometer, thermogravimetric analysis, dynamic mechanical analysis, universal testing machine and laser confocal microscopy. The test results demonstrated that the incorporation of WCO declined the viscosity and extended the allowable construction time of the unmodified EAR binder. The inclusion of WCO improved the compatibility between asphalt and crumb rubber and the damping ability and elongation at the break of the unmodified EAR binder. The presence of WCO had a marginal effect on the thermal stability of the unmodified EAR binder. Confocal microscopy observation revealed that asphalt rubber particles aggregated in the epoxy phase of the unmodified EAR binder. With the inclusion of WCO, co-continuous asphalt rubber particles became more spherical.

Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.

Water-Soluble Conjugated Polymer as a Fluorescent Probe for Monitoring Adenosine Triphosphate Level Fluctuation in Cell Membranes during Cell Apoptosis and in Vivo.

Adenosine triphosphate (ATP) is used as the energy source in cells and plays crucial roles in various cellular events. The cellular membrane is the protective barrier for the cytoplasm of living cells and involved in many essential biological processes. Many fluorescent probes for ATP have been successfully developed, but few of these probes were appropriate for visualizing ATP level fluctuation in cell membranes during the apoptotic cell death process. Herein, we report the synthesis of a new water-soluble cationic polythiophene derivative that can be utilized as a fluorescent sensor for detecting ATP in cell membranes. Poly((3-((4-methylthiophen-3-yl)oxy)propyl)triphenylphosphonium chloride) (PMTPP) exhibits high sensitivity and good selectivity to ATP, and the detection limit is 27 nM. The polymer shows low toxicity to live cells and excellent photostability in cell membranes. PMTPP was practically utilized for real-time monitoring of ATP levels in the cell membrane through fluorescence microscopy. We have demonstrated that the ATP levels in cell membranes increased during the apoptotic cell death process. The probe was also capable of imaging ATP levels in living mice.

Biohybrid Flexible Sperm-like Microrobot for Targeted Chemo-Photothermal Therapy.

Magnetic micro/nanorobots are promising platforms for targeted drug delivery, and their construction with soft and flexible features has received extensive attention for practical applications. Despite significant efforts in this field, facile fabrication of magnetic microrobots with flexible structures and versatility in targeted therapy remains a big challenge. Herein, we proposed a novel universal strategy to fabricate a biohybrid flexible sperm-like microrobot (BFSM) based on a Chlorella (Ch.) cell and artificial flagella, which showed great potential for targeted chemo-photothermal therapy for the first time. In this approach, microspherical Ch. cells were utilized to construct the microrobotic heads, which were intracellularly deposited with core-shell Pd@Au, extracellularly magnetized with Fe3O4, and further loaded with anticancer drug. The magnetic heads with excellent photothermal and chemotherapeutic capability were further assembled with flexible polypyrrole nanowires via biotin-streptavidin bonding to construct the BFSMs. Based on the exquisite head-to-tail structures, the BFSMs could be effectively propelled under precessing magnetic fields and move back and forth without a U-turn. Moreover, in vitro chemo-photothermal tests were conducted to verify their performance of targeted drug delivery toward localized HeLa cells. Due to this superior versatility and facile fabrication, the BFSMs demonstrated great potential for targeted anticancer therapy.

Meta-analysis of the association between chronic periodontitis and chronic kidney disease.

BACKGROUND: Many scholars have performed several clinical studies have investigated the association between chronic periodontitis (CP) and chronic kidney disease (CKD). However, there are still differences between these research results, and there is no unified conclusion. Therefore, a systematic review is required to understand this issue fully. AIM: To explore the correlation between CP and CKD. METHODS: Literature on the correlation between CP and CKD, as well as the clinical attachment level (CAL) and pocket probing depth (PPD) of CKD and non-CKD, were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science repositories until January 2024. After the effective data were extracted, data processing and statistics were performed using Stata 12.0. RESULTS: Of the 22 studies, 13 were related to CP and CKD, and 9 reported CAL and PPD in patients with CKD and healthy controls. Meta-analysis of the correlation between CP and CKD revealed that CKD probability in people with CP was 1. 54 times that of healthy individuals [relative risk = 1.54, 95% confidence interval (CI): 1.40-1.70], and CP incidence in patients with CKD was 1. 98 times that of healthy individuals [overall risk (OR) = 1.98, 95%CI: 1.53-2.57]. Meta-analysis of CAL and PPD evaluations between CKD patients and healthy individuals showed that CAL and PPD levels were higher in CKD patients [standard mean difference (SMD) of CAL = 0.65, 95%CI: 0.29-1.01; SMD of PPD = 0.33, 95%CI: 0.02-0.63]. CONCLUSION: A bidirectional association exists between CP and CKD. CKD risk is increased in CP patients and vice versa. Periodontal tissue or tooth loss risks increase over time in CKD patients.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice.

This study aimed to investigate the effect of periostin (PN) on the expression of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), microtubule-associated protein1 light chain 3B (LC3B), and Beclin1 in mouse alveolar bone specimens and cultured osteoblasts in vitro, to preliminarily explore the role of PN and autophagy in remodeling bone metabolism during tooth eruption. Mice at 5 days of age were injected with 75 ng/mL recombinant PN protein under the periosteum for 3 consecutive days according to the standard of 1 mL/100 g/day. Then, their mandibles were removed, and the expression of bone metabolic and autophagy factors was detected by immunohistochemistry. Mouse osteoblast-like cells cultured in vitro were treated with recombinant PN at a concentration of 75 ng/mL. The changes in the aforementioned indicators were compared again by immunofluorescence and western blotting 72 h after dosing. The results of the mouse samples showed that the protein expression of RANKL, LC3B, and Beclin1 decreased, accompanied by the decrease in RANKL/OPG ratio. However, OPG protein expression increased in the dosing group. Immunofluorescence and western blotting results of osteoblasts cultured in vitro showed that the protein expression of RANKL, LC3B, Beclin1, and the RANKL/OPG ratio in the experimental group decreased, but OPG expression increased. PN may regulate alveolar bone metabolism during tooth eruption by inhibiting the RANKL/OPG ratio and autophagy, which will provide a new research perspective for further exploration of the mechanisms during tooth eruption.

Floating assembly of diatom Coscinodiscus sp. microshells.

Diatoms have silica frustules with transparent and delicate micro/nano scale structures, two dimensional pore arrays, and large surface areas. Although, the diatom cells of Coscinodiscus sp. live underwater, we found that their valves can float on water and assemble together. Experiments show that the convex shape and the 40 nm sieve pores of the valves allow them to float on water, and that the buoyancy and the micro-range attractive forces cause the valves to assemble together at the highest point of water. As measured by AFM calibrated glass needles fixed in manipulator, the buoyancy force on a single floating valve may reach up to 10 µN in water. Turning the valves over, enlarging the sieve pores, reducing the surface tension of water, or vacuum pumping may cause the floating valves to sink. After the water has evaporated, the floating valves remained in their assembled state and formed a monolayer film. The bonded diatom monolayer may be valuable in studies on diatom based optical devices, biosensors, solar cells, and batteries, to better use the optical and adsorption properties of frustules. The floating assembly phenomenon can also be used as a self-assembly method for fabricating monolayer of circular plates.

Magnetic Biohybrid Microrobot Multimers Based on Chlorella Cells for Enhanced Targeted Drug Delivery.

Magnetic micro-/nanorobots have been regarded as a promising platform for targeted drug delivery, and tremendous strategies have been developed in recent years. However, realizing precise and efficient drug delivery in vivo still remains challenging, in which the versatile integration of good biocompatibility and reconfiguration is the main obstacle for micro-/nanorobots. Herein, we proposed a novel strategy of magnetic biohybrid microrobot multimers (BMMs) based on Chlorella (Ch.) and demonstrated their great potential for targeted drug delivery. The spherical Ch. cells around 3-5 µm were magnetized with Fe3O4 to fabricate biohybrid microrobots and then loaded with doxorubicin (DOX). Using magnetic dipolar interactions, the microrobot units could reconfigure into chain-like BMMs as tiny dimers, trimers, and so forth via attraction-induced self-assembly and disassemble reversibly via repulsion. The BMMs exhibited diverse swimming modes including rolling and tumbling with high maneuverability, and the rolling dimer's velocity could reach 107.6 µm/s (∼18 body length/s) under a 70 Gs precessing magnetic field. Furthermore, the BMMs exhibited low cell toxicity, high DOX loading capacity, and pH-triggered drug release, which were verified by chemotherapy experiments toward HeLa cancer cells. Due to the remarkable versatility and facile fabrication, the BMMs demonstrate great potential for targeted anticancer therapy.

Efficient removal of nano- and micro- sized plastics using a starch-based coagulant in conjunction with polysilicic acid.

Microplastic (MP) pollution has increasingly become an enormous global challenge due to the ubiquity and uncertain environmental performance, especially for nano- and micro- sized MPs. In this work, the performance and mechanisms in coagulation of 100 nm-5.0 µm sized polystyrene particles using an etherified starch-based coagulant (St-CTA) assisted by polysilicic acid (PSA) were systematically studied on the basis of the changes in MPs removal rates under various pH levels and in the presence of different coexisting inorganic and organic substances, zeta potentials of supernatants, and floc properties. St-CTA in conjunction with PSA had a high performance in coagulation of nano- and micro- sized MPs from water with a lower optimal dose and larger and compacter flocs. Besides, the MPs removal rate can be improved in acidic and coexisting salt conditions. The efficient performance in removal of MPs by this enhanced coagulation was owing to the synergic effect, that is, the effective aggregation of MPs through the charge neutralization of St-CTA followed by the efficient netting-bridging effect of PSA. The effectiveness of this enhanced coagulation was further confirmed by removal of two other typical nano-sized MPs, such as poly(methyl methacrylate) and poly(vinyl chloride), from different water sources including tap water, river water, and sludge supernatant from a sewage treatment plant. This work provided a novel enhanced coagulation technique that can effectively remove nano- and micro- sized MPs from water.

Zein-polycaprolactone core-shell nanofibers for wound healing.

In a previous study, we developed electrospun antimicrobial microfiber scaffolds for wound healing composed of a core of zein protein and a shell containing polyethylene oxide. While providing a promising platform for composite nanofiber design, the scaffolds showed low tensile strengths, insufficient water stability, as well as burst release of the antimicrobial drug tetracycline hydrochloride, properties which are not ideal for the use of the scaffolds as wound dressings. Therefore, the aim of the present study was to develop fibers with enhanced mechanical strength and water stability, also displaying sustained release of tetracycline hydrochloride. Zein was chosen as core material, while the shell was formed by the hydrophobic polymer polycaprolactone, either alone or in combination with polyethylene oxide. As compared to control fibers of pristine polycaprolactone, the zein-polycaprolactone fibers exhibited a reduced diameter and hydrophobicity, which is beneficial for cell attachment and wound closure. Such fibers also demonstrated sustained release of tetracycline hydrochloride, as well as water stability, ductility, high mechanical strength and fibroblast attachment, hence representing a step towards the development of biodegradable wound dressings with prolonged drug release, which can be left on the wound for a longer time.

Effect of periostin silencing on Runx2, RANKL and OPG expression in osteoblasts.

OBJECTIVE: Normal tooth eruption is closely related to relevant genes and the dynamic balance between osteoblasts and osteoclasts. If secretion of RANKL and OPG by osteoblasts is disordered, relevant gene deficiencies or mutations will result in serious tooth eruption disturbances, e.g., cleidocranial dysplasia (CCD). Thus, we examined changes in Runx2, RANKL, and OPG protein expression in MC3T3-E1 cells after silencing the periostin gene, thus, providing an experimental basis to study tooth eruption mechanisms. METHODS: Based on previous research, cells were divided into two groups according to the virus number: the contrast group (NC group; pFU-GW-016 PSC53349-1) and the experimental group (KD group; LVpFU-GW-016PSC66473-1). Cells were infected with the lentiviral vector (multiplicity of infection = 100) and assessed by image cytometry 72 h after infection. After screening cells for the strongest gene silencing effect, Runx2, RANKL and OPG protein expression were detected by western blotting. RESULTS: Based on quantitative PCR, the periostin gene silencing efficiency in the KD group was over 90% (P < 0.01). After periostin gene silencing, compared with the control group, Runx2 and RANKL expression in the KD group was reduced (P < 0.01 and P < 0.05, respectively), but OPG protein expression showed no significant change (P > 0.05). The RANKL/OPG ratios in the KD group were lower than those in the NC group after periostin gene silencing (P < 0.05). CONCLUSIONS: Silencing periostin may reduce the expression of Runx2, suggesting that there may be a synergistic relationship between periostin and Runx2 in their effects on osteoblast differentiation, while reducing RANKL expression obviously confirms that the NF-κB (nuclear factor κB) pathway plays an important role in this process and that periostin silencing changes the underlying tendency toward bone metabolism. This method could even provide an experimental basis for using exogenous periostin protein to treat some abnormal bone metabolism diseases, as it could be used as a supplement for the treatment of tooth eruption abnormalities caused by Runx2 gene deficiencies or mutations (CCD).

Removal of fluoroquinolone antibiotics using actinia-shaped lignin-based adsorbents: Role of the length and distribution of branched-chains.

A series of actinia-shaped lignin-based adsorbents (LNAEs) featuring lignin(LN) as the core and grafted poly(acrylic acid) (PAA) as the tentacle were designed and fabricated. LNAEs were applied to remove ofloxacin and ciprofloxacin from water, and their maximum adsorption capacities were 0.835 and 0.965 mmol/g at pH 6.0, respectively. However, their adsorption capacities were up to about 20 % and 31 % reductions in the present of NaCl and humic acid, respectively. Electrostatic attraction (EA) and hydrogen bonding (HB), including ordinary HB and negative charged auxiliary HB, were mainly involved in adsorption. Experimental and calculation results indicated HB contributes more than EA. The effects of two structural factors of LNAEs, namely, PAA branched-chain length(L) and distribution density(D), on the adsorption performance associated with HB and EA, were quantitatively discussed using a binary nonlinear model based on phenomenological theory. The fitting results were completely consistent with the experimental findings. D was more efficient than L in promoting HB and EA in adsorption due to the cooperative effects of adjacent branched-chains and enhanced activity of terminal groups. This study provides a better understanding of the structure-activity relationship of surface grafting-modified adsorbents and fundamental guidance for the exploitation and design of novel and efficient adsorbents.

An Investigation of Softening Laws and Fracture Toughness of Slag-Based Geopolymer Concrete and Mortar.

This paper aimed to determine the softening laws and fracture toughness of slag-based geopolymer (SG) concrete and mortar (SGC and SGM) as compared to those of Portland cement (PC) concrete and mortar (PCC and PCM). Using three-point bending (TPB) tests, the load vs. mid-span displacement, crack mouth opening displacement, and crack tip opening displacement curves (P-d, P-CMOD, and P-CTOD curves) were all recorded. Bilinear softening laws of the PC and SG series were determined by inverse analysis. Furthermore, the cohesive toughness was predicted using an analytical fracture model. The cohesive toughness obtained by experimental study was consistent with that predicted by analytical method, proving the correctness of the tension softening law obtained from inverse analysis. In addition, both initial and unstable fracture toughness values of SG mortar were lower than those of PC mortar given the same compressive strength. Moreover, the initial fracture toughness of SG concrete was generally lower than that of PC concrete, whereas the unstable fracture toughness exhibited an opposite trend.

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma.

Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m2 (day 1), gemcitabine 1 g/m2 (days 1 and 8) and oxaliplatin 130 mg/m2 (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

Effect of Periostin Silencing on the Autophagy of Osteoblasts.

The objective of the present work was to investigate the effect of Periostin (POSTN) silencing on autophagy in osteoblasts, and provide an experimental basis for studying the mechanism of dental eruption. The cells were divided into the following four groups according to their viral number: the NC group, pFU-GW-016PSC53349-1; group KD1, LVpFU-GW-016PSC66471-1; group KD2, LVpFU-GW-016PSC66472-1; and group KD3, LVpFU-GW-016PSC66473-1. The lentiviral vector was infected at MOI = 100 in the ENi.S medium containing 5 g/mL Polybrene. The target gene expression was observed by a Celigo® Image Cytometer at 72 hours after infection, and the positive rate of fluorescence was noted. A two-step method of quantitative real-time PCR (qRT-PCR) was used to detect the silencing effect of POSTN. Western blotting was then performed to assess the expression of autophagy-related proteins Beclin-1 and LC3 in the group showing the best gene silencing effects. The experimental results showed that there was strong green fluorescence in group KD3. As confirmed via qRT-PCR analysis, the POSTN silencing efficiency in group KD3 reached 92.1%. The Western blotting revealed that the expression of Beclin-1 protein in group KD3 was significantly higher than that in the NC group. However, the LC3 protein expression was not significantly different from that of the control group. The lentiviral vector targeting POSTN in osteoblasts was constructed successfully. In addition, the expression of autophagy protein in mouse osteoblasts increased after POSTN silencing. This finding may provide new approaches for understanding the molecular signal transduction of POSTN during the tooth eruption process.