3D porous conductive matrix based on phase-transited BSA and covalent coupling-stabilized transition ZnS-CNT for antifouling and on-site detection of nitrite in soil.

Nitrite plays a critical role in a variety of nitrification and denitrification processes in the nitrogen cycle. Due to the high surface energy, tendency to aggregate, and poor conductivity, current nitrite ZnS-based sensing platform could not meet the need of on-site nitrite detection in smart agriculture. In order to address these issues, the carboxylated carbon nanotube (CNT) was introduced to reduce the surface energy and prevented aggregation of ZnS, while ZnS-carboxylated CNT (ZnS-CNT) composite also provided excellent electrochemical conductivity. Furthermore, the introduction of phase transition BSA (PTB) created a three-dimensional porous conductive matrix without interfering with the mass transfer process of nitrite. The resulting sensing platform exhibited a linear detection range of 10 nM to 0.4 mM for nitrite, with a detection limit of 0.73 nM. And this sensing platform had the excellent antifouling ability to direct detection nitrite in real soil suspension. In addition, the sensing platform demonstrated remarkable resistance to interferences from pH variations, microbial presence, and organic pollutants that usually present in soil environment. Therefore, on-site detection of nitrite ions in soil environment was realized no needing complex pretreatments.

Combination of chidamide and PD-1 blockade in Refractory/Relapsed aggressive large B-cell lymphomas with high risk of failing CAR-T therapy.

BACKGROUND: Refractoriness and relapse after chimeric antigen receptor T-cell therapy have emerged as major challenges for immunotherapy of aggressive large B-cell lymphoma. Thus far, there is no consensus on how to address treatment failure and whether to administer maintenance therapy following CAR-T cell therapy. METHODS: From August 2017 through November 2022, 52 patients with refractory/relapsed aggressive LBCL who had a high risk of resistance to CAR-T cell therapy were given chidamide in combination with a PD-1 inhibitor as maintenance therapy following either CAR19/22 T-cell cocktail therapy or CAR19/22 T-cell cocktail therapy plus autologous stem cell transplantation (ASCT). Another 52 aggressive LBCL patients who had comparable baseline characteristics and received similar therapeutic regimens but did not receive any interventions following CAR-T cell therapy or CAR-T cell therapy plus ASCT were regarded as the control group to evaluate the efficacy and safety of the combination of chidamide and a PD-1 inhibitor. RESULTS: Among the 52 patients who received chidamide and a PD-1 inhibitor as maintenance therapy, with a median follow-up of 26.5 months (range: 1.1-53.8), neither the median progression-free survival (PFS) nor overall survival (OS) was reached, and the expected 2-year OS and PFS rates were 89 % and 77 %, respectively, which were superior to those of the control group (p < 0.001). Long-term chidamide administration and a specific genetic subtype of EZB were strongly associated with a better response after chidamide plus PD-1 blockade therapy. Additionally, long-term chidamide administration was significantly associated with prolonged persistence and reactivation of CD19-directed CAR-T cells in the peripheral blood. Adverse effects (AEs) were moderate and reversible, and no treatment-related deaths occurred. CONCLUSION: Our results indicate that the combination of chidamide and PD-1 blockade as maintenance therapy could improve the outcomes of aggressive LBCL patients at high risk of failing CAR-T cell therapy.

TNF-α is a predictive marker in distinguishing myeloproliferative neoplasm and idiopathic erythrocytosis/thrombocytosis: development and validation of a non-invasive diagnostic model.

Purpose: Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) exhibit phenotypic similarities with JAK/STAT-unmutated idiopathic erythrocytosis and thrombocytosis (IE/IT). We aimed to develop a clinical diagnostic model to discern MPN and IE/IT. Methods: A retrospective study was performed on 77 MPN patients and 32 IE/IT patients in our center from January 2018 to December 2023. We investigated the role of hemogram, cytokine and spleen size in differentiating MPN and IE/IT among newly onset erythrocytosis and thrombocytosis patients. Independent influencing factors were integrated into a nomogram for individualized risk prediction. The calibration and discrimination ability of the model were evaluated by concordance index (C-index), calibration curve. Results: MPN had significantly higher TNF-α level than IE/IT, and the TNF-α level is correlated with MF-grade. Multivariable analyses revealed that TNF-α, PLT count, age, size of spleen were independent diagnostic factors in differentiating MPN and IE/IT. Nomograms integrated the above 4 factors for differentiating MPN and IE/IT was internally validated and had good performance, the C-index of the model is 0.979. Conclusion: The elevation of serum TNF-α in MPN patients is of diagnostic significance and is correlated with the severity of myelofibrosis. The nomogram incorporating TNF-α with age, PLT count and spleen size presents a noteworthy tool in the preliminary discrimination of MPN patients and those with idiopathic erythrocytosis or thrombocytosis. This highlights the potential of cytokines as biomarkers in hematologic disorders.

Optimization of degradation conditions and analysis of degradation mechanism for nitrite by Bacillus aryabhattai 47.

Excessive nitrite levels cause significant damage to aquaculture, making it crucial to explore green and reliable nitrite removal technologies. In this study, A Bacillus aryabhattai (designated as the strain 47) isolated from aquaculture wastewater was used as the experimental strain. The nitrite degradation conditions of the strain 47 were optimized, and the optimal conditions are: glucose was 12.74 g/L, fermented special soybean meal was 21.27 g/L, MgCl2 369 mg/L, pH 7.0, incubated at 30 °C with the inoculum size of 2 % and the rotation speed of 170 rpm. Under the optimal conditions, the nitrite concentration of the culture solution was 200 mg/L, and the nitrite removal rate reached 91.4 %. Meanwhile, the mechanism by which Mg2+ enhanced the nitrite degradation ability of the strain 47 was investigated by transcriptomics. An operon structure directed cellular trafficking of Mg2+, and then, the Mg2+-mediated catalytic reaction of multiple enzymes enhanced and improved cellular metabolic processes (e.g. the transport and metabolism of nitrite, central carbohydrate metabolism oxidative phosphorylation). At the same time, with the progress of cell metabolism, cells secreted a series of enzymes related to nitrite transport and metabolism to promote the metabolism of nitrite. And the process of the assimilated nitrate reduction pathway of nitrite degradation in the strain 47 was elaborated at the transcriptome level. This study provided a new insight into nitrite treatment mediated by microbial organisms.

Sodium Dodecyl Sulfate-Adjusted Phase Composition of Hydrated Tungsten Oxides as Stable Self-Supporting Electrodes for Supercapacitors with High Volumetric Specific Capacitance.

High pseudocapacitive activity of hydrated tungsten oxides (WO3·xH2O, x = 1 or 2) makes them promising materials for supercapacitors (SCs). During their synthesis, additives such as complexing agents and surfactants generally can only affect the morphology and/or size of the products. Here, we demonstrate that not only morphology and size of WO3·xH2O were affected, its phase composition could also change from WO3·2H2O to WO3·H2O simply by increasing the amount of sodium dodecyl sulfate (SDS) during its anodization synthesis. To the best of our knowledge, such a phenomenon has not been reported before. In addition, SDS introduced a special structure to the products, i.e., WO3·xH2O nanoplatelets constructed from nanoparticle multilayers with abundant nanogaps between the multilayers, which further arranged into nanoflowers with increased amounts of SDS. Benefiting from such a structure, low internal resistance, enhanced stability, and fast redox kinetics, the as-obtained WO3·xH2O/W-3 self-supporting electrode showed a high volumetric specific capacitance of 1402.92 F cm-3 and good cycling stability (a capacity retention of 106% after 10 000 cycles). In addition, an all-solid-state asymmetric SC device based on WO3·xH2O/W-3 delivered high a volumetric energy density of 44.0 mW h cm-3 at 0.5 W cm-3. Our method demonstrates a potential way to fabricate excellent self-supporting electrodes for SCs.

Soliton rain in all-polarization-maintaining mode locked fiber laser.

For the first time the phenomenon of soliton rain is observed in a mode-locked fiber laser with all-polarization-maintaining (all-PM) architecture. The laser is mode-locked using a semiconductor saturable absorber mirror (SESAM) and operates in the all-normal dispersion (ANDi) regime. The operation state of the laser can be switched from dissipative soliton to soliton rain by simply raising the pump power, without any manipulation of the intracavity polarization state given that all components of the resonator are made of PM fibers. The soliton rain generated in the laser is self-starting and replicable, since it occurs in every individual operation of the laser as the pump power is increased to an approximately invariant value.

MPC-ESO Position Control Strategy for a Miniature Double-Cylinder Actuator Considering Hose Effects.

Miniature hydraulic actuators are especially suitable for narrow-space and harsh environment arrangement. However, when using thin and long hoses to connect components, the volume expansion caused by pressurized oil inside can have significant adverse effects on the performance of the miniature system. Moreover, the volumetric variation relates to many uncertain factors that are difficult to describe quantitatively. This paper conducted an experiment to test the hose deformation characteristics and presents the Generalized Regression Neural Network (GRNN) to describe the hose behavior. On this basis, a system model of a miniature double-cylinder hydraulic actuation system was established. To decrease the impact of nonlinearity and uncertainty on the system, this paper proposes a Model Predictive Control (MPC) based on Augmented Minimal State-Space (AMSS) model and Extended State Observer (ESO). The extended state space acts as the prediction module model for the MPC, and the disturbance of the ESO estimates is fed to the controller to improve the anti-disturbance capability. The full system model is validated by comparison between the experiment and the simulation. For a miniature double-cylinder hydraulic actuation system, the proposed MPC-ESO control strategy contributes to a better dynamic than conventional MPC and fuzzy-PID. In addition, the position response time can be reduced by 0.5 s and achieves a 4.2% reduction in steady-state error, especially for high-frequency motion. Moreover, the actuation system with MPC-ESO exhibits better performance in suppressing the influence of the load disturbance.

Superresolution Fluorescence Microscopy of Platelet Subcellular Structures as a Potential Tumor Liquid Biopsy.

Blood-based tumor liquid biopsies are promising as an alternative or complement to tissue biopsies due to their noninvasiveness, convenience, and safety, and there is still a great demand for the discovery of new biomarkers for these biopsies. Here, nanoscale distribution patterns of subcellular structures in platelets, as imaged by structured illumination superresolution fluorescence microscopy, as a new type of potential biomarker for tumor liquid biopsies are presented. A standardized protocol for platelet sample preparation and developed an automated high-throughput image analysis workflow is established. The diagnostic capability based on the statistical analysis of 280 000 superresolution images of individual platelets from a variety of tumor patients, benign mass patients, and healthy volunteers (n = 206) is explored. These results suggest that the nanoscale distribution patterns of α-granules in platelets have the potential to be biomarkers for several cancers, including glioma and cervical, endometrial, and ovarian cancers, facilitating not only diagnosis but also therapeutic monitoring. This study provides a promising novel type of platelet parameter for tumor liquid biopsies at the subcellular level rather than the existing cellular or molecular level and opens up a new avenue for clinical applications of superresolution imaging techniques.

Coupling Characteristics of Powder and Laser of Coaxial Cone Nozzle for Laser Direct Metal Deposition: Numerical Simulation and Experimental Study.

Laser direct metal deposition (LDMD) enables not only the preparation of high-performance coatings on the surfaces of low-property materials but also the three-dimensional direct manufacturing and re-manufacturing of parts. In the LDMD process, the spatial coupling characteristics of the powder flow and the laser beam are the key factors affecting the forming quality of the cladding layer. Based on the gas-solid two-phase flow theory, a numerical model of coaxial powder feeding was established by CFD. The powder flow characteristics of the lower part of the nozzle, the powder particle motion trajectory, and the optical-powder spatial coupling morphology and law were studied, and the relationship between the powder flow morphology, laser beam, and powder utilization was explored. On this basis, the law between the optical-powder coupling characteristics and the geometric characteristics of the cladding layer is discussed in conjunction with LDMD experiments. The results show that the powder concentration scalar located in the focal plane of the laser beam can be used to visualize the optical-powder coupling morphology. When the powder feeding speed exceeds the loading capacity of the carrier gas flow, the powder concentration in the center of the spot and the powder utilization rate decrease. When the carrier gas flow rate is 4.0 L/min and the powder feeding rate is 4.0 g/min, the best utilization rate achieved is 81.4%. In addition, the H (height) of the cladding layer is more sensitive to changes in the powder concentration than the W (width). These findings provide new ideas for nozzle structure design and the optimization of LDMD parameters.

Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data.

Background: Central nervous system lymphoma (CNSL) is considered an aggressive lymphoma with a poor prognosis. Studies investigating CNSL have shown that chimeric antigen receptor (CAR) T-cell therapy has demonstrated an effective response in limited sample sizes. Therefore, we conducted this systematic review and meta-analysis to clarify the sustained efficacy and factors associated with the sustained efficacy of CAR T-cell therapy in the treatment of CNSL. Methods: We searched studies from PubMed, Embase, Medline, and the Cochrane Center Register of Controlled Trials up to July 2023. Studies that included individual data on the duration of response (DoR) after receiving CAR T-cell therapy were enrolled. Pooled response rates were calculated using fixed-effects or random-effects models. Subgroup analysis was performed to analyze the heterogeneity, and a Cox regression model was performed to identify the factors associated with sustained efficacy. Results: In total, 12 studies including 69 patients were identified and included in this meta-analysis. The pooled relapse rate was 45% [95% CI 35, 56]. Subgroup analyses of relapse rates revealed that CAR T-cells using the CD28/4-1BB domain (CD28/4-1BB vs. CD28 vs. 4-1BB, p = 0.0151), parenchymal or leptomeningeal involvement (parenchymal or leptomeningeal vs. both parenchymal and leptomeningeal, p < 0.0001), and combined treatment with CAR T-cell therapy [Autologous stem cell transplantation (ASCT) plus CAR T-cell therapy vs. CAR T cells with maintenance therapy vs. CAR T-cell therapy alone, p = 0.003] were associated with lower relapse rates in patients. Time-to-event endpoints were assessed using reconstructed individual patient survival data to explore key modulators of DoR. Partial response status at CAR-T infusion and the use of ASCT plus CAR T-cell therapy were associated with longer DoR at the multivariate level, with hazard ratios of 0.25 and 0.26, respectively. Conclusion: CAR T-cell therapy shows promising and sustained efficacy in CNSL patients. However, further prospective large-scale studies are needed to assess these effect modifiers to optimize patient selection and improve the sustained efficacy of CAR T-cell therapy in the treatment of CNSL. Systematic review registration: https://clinicaltrials.gov/, identifier PROSPERO CRD42023451856.

Flexibility and fragmentation aware routing, core and spectrum allocation for hybrid AoD nodes in SDM-EONs.

Space division multiplexing elastic optical network (SDM-EON) enables high-capacity transmission, in which the network nodes should provide high switching flexibility while limiting the complexity and costs of nodes. Architecture on demand (AoD) nodes can meet these requirements but the slow configuration time of optical backplane in AoD nodes makes it difficult to serve latency-sensitive requests. In this paper, we propose a hybrid optical backplane based on micro-electromechanical systems (MEMS) and semiconductor optical amplifier (SOA) switches to provide fast configuration time for AoD nodes. Moreover, we propose quantitative measures of node switching flexibility in SDM-EONs and of link configuration speed in AoD nodes. Based on the hybrid backplane architecture and the measurement approaches, we propose a flexibility and fragmentation aware routing, spectrum and core allocation algorithm and an AoD synthesis algorithm. Simulation results show that the hybrid AoD nodes with support of spatial lane change can reduce network blocking probability. The AoD based on this hybrid backplane structure can improve the network performance by 32.8% compared to the AoD based on the traditional MEMS. Compared with traditional reconfigurable optical add/drop multiplexers (ROADMs), the hybrid AoD nodes can control the number of wavelength selective switch (WSS) ports.

Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.

Trastuzumab is a standard molecular targeted therapy for human epidermal growth factor receptor 2(HER2) -positive breast cancer, which can significantly improve the survival of patients with this molecular subtype of breast cancer. However, the clinical problem of onset or secondary resistance to trastuzumab has limited its efficacy. Therefore, it is very important to explore the mechanism of trastuzumab resistance and formulate countermeasures. Our study described the underlying molecular mechanism of trastuzumab resistance including ERBB2 mutations and nuclear localization, transcriptional and post-translational alterations of ERBB2, over-activation of bypass signaling pathways activation and so on. Then summarize the potential emerging predicting biomarkers and therapeutic strategies for trastuzumab resistance, in order to provide research direction for reversing trastuzumab resistance.

Tuberculosis infection related hemophagocytic lymphohistiocytosis diagnosed in patient with GZMB mutation: A case report and literature review.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome associated with infections, tumors and connective tissue disease. However rapid identification of the underlying infectious cause of HLH is challenging because traditional etiological diagnostics are time-consuming and sometimes fail to identify the pathogens. Metagenomic next-generation sequencing (mNGS) may be a potential optimal solution, which may help improve the clinical diagnosis of underlying infections in hematological diseases. CASE PRESENTATION: A 28-year-old man presented with a 2-month history of intermittent fever and cytopenia. The HLH was diagnosed based on the manifestations of fever, splenomegaly, anemia, thrombocytopenia, hyperferritinemia, hyperglyceridemia, and elevated IL-2R levels. High-through-put sequencing analysis detected a GZMB mutation. While the initial detection of cultures and smears of tuberculosis was negative, TB infection was eventually identified by mNGS of blood sample. The symptoms rapidly abated during the initial administration of TB. CONCLUSION: The present case proposed that mNGS might be an effective diagnostic tool for diagnosing rare infectious cause of secondary HLH. GZMB mutation was first discovered to be present in secondary HLH.

An indirect detection strategy-assisted self-cleaning electrochemical platform for in-situ and pretreatment-free detection of endogenous H2S from sulfate-reducing bacteria (SRB).

The endogenous hydrogen sulfide (H2S) can be adopted as an indicator for the indirect detection of sulphate-reducing bacteria (SRB), which considered to be closely related to pipeline corrosion and human intestinal health. Unfortunately, the in-situ detection of endogenous H2S from SRB in the complex culture medium still faces huge challenges. Besides nonspecific adsorption from the culture medium of SRB, the problem of electrode passivation by produced elemental sulfur during electrochemical detection processes of H2S cannot be ignored. To address these challenges, herein a synergistic sensing platform based on self-cleaning electrode interface and indirect detection strategy (specific H2S-induced chemical reaction) is developed. This indirect sensing strategy-assisted self-cleaning electrochemical platform showed a relatively good linear response toward H2S in the range of 0.5 - 5 µM, and the corresponding limit of detection (LOD) was calculated to be 5.09 nM. More importantly, the satisfactory self-cleaning electrode interface in indirect detection system (with only a 4.10% decrease in signal over 50 electrochemical repeated cycles) showed the electrode surface not being disturbed by elemental sulfur. Furthermore, this good selectivity of the indirect detection strategy in combination with the reproducibility, stability, and antifouling activity of the self-cleaning interface, enabled a synergistic sensing platform to detect H2S directly in the complex culture medium of SRB without time-consuming sample pretreatments. Moreover, this proposed construction strategy of synergetic sensing platform could be explored to other endogenous molecules in complex environment based on different antifouling materials and specific reactions.

Dual aggregation in ground state and ground-excited state induced by high concentrations contributes to chlorophyll stability.

Chlorophyll (Chl) has great application potential in food colouring and nutritional supplementation. Since Chl is easily degraded, stability protection is vital to its application. Herein, a dual aggregation mechanism induced by high concentrations to improve Chl stability was proposed. As a result, the Chl retention at high concentrations increased to 323.92% of that at low concentrations. To explain aggregation, the Chl dimer was observed by atomic force microscopy, and a stable structural model of the Chl a "sandwich" dimer was established. It was proven that Chl dimer stability was dominated by van der Waals (vdW) interactions, while monomer orientation during aggregation was dominated by electrostatic interactions. Charge transfer (CT) was also shown to be a key interaction in the dimer. Excitation at 393 nm was first proposed for CT identification. This research hopes to provide new ideas for the design of food ingredients in human health promotion.

Aggregation induced by the synergy of sodium chloride and high-pressure improves chlorophyll stability.

The development of green vegetable processing is still limited by the imperfect green protection now. Chlorophyll (Chl), the main pigment presented in green vegetables, was studied that the effects of NaCl on the stability of it, and the synergy of NaCl and high-pressure on Chl protection. Compared to the control, the retention of Chl was increased by 80.14% and the activation energy was 62.7% higher in 7.8% NaCl solution. When the pressure was 600 MPa with 7.8% NaCl, the synergy of NaCl and high-pressure increased the Chl retention by 100%. The restriction of NaCl to H2O provided Chl with a lower polarity environment and increased the contact between Chl molecules. And the fluorescence quenching confirmed the aggregation of Chls induced by high-pressure. This study explains the mechanism of green protection by NaCl and high-pressure, broadening the horizon for the development of color protection in vegetable processing.

Synthesis and antiviral effect of phosphamide modified vidarabine for treating HSV 1 infections.

Vidarabine (ARA) was one of the earliest marine-related compounds to be used clinically for antiviral therapy, however, its fast metabolism is the main defect of this drug. To overcome this, we designed and synthesized a group of phosphamide-modified ARA compounds using ProTide technology. With a phosphamide modification, these compounds could become the substrate of specific phospholipase enzymes expressed in the liver. Among all 16 synthesized compounds, most showed stronger activity against herpes simplex virus type 1 (HSV-1) than ARA (EC50 of approximately 10 µM). The top three compounds were compound 2 (EC50 = 0.52 ± 0.04 µM), compound 6 (EC50 = 1.05 ± 0.09 µM) and compound 15 (EC50 = 1.18 ± 0.08 µM) (about 2 times higher than Sp type compound 2). This study provides evidence for use of the phosphamide modification, which could give ARA higher activity and liver cell targeting.

A novel ratiometric electrochemical cupric ion sensing strategy based on unmodified electrode.

In this paper, a novel ratiometric electrochemical Cu(II) sensing strategy was established by monitoring the changes of the reduction peaks of Cu(II) and paracetamol based on bare electrode. The paracetamol was adopted as an optimal ratiometric reference (rather than classic ferrocene (Fc) and methylene blue (MB)) due to its highly stability and suitable reduction peak, which is well-separated from the reduction peak of Cu(II). Adopting paracetamol as the internal reference, the reproducibility of this sensing strategy was obviously enhanced. The sensing platform is very cheap in cost and avoids some time-consuming electrode modification process, which is helpful for low-cost and rapid detection.

Highly stretchable composites based on cellulose.

Cellulose is a kind of natural polymer with good biocompatibility, biodegradability, non-toxicity, low cost and other advantages, which has been widely used in many fields, such as energy, biological scaffolds, medicine, paper making, cosmetics, and template materials. Based on this, how to use cellulose to construct stretchable composites to meet the needs of different fields has attracted widespread attention. In this review, we have described the applications of cellulose-based stretchable composites, including sensor applications, energy applications, bionic and medical materials applications, fabric applications, and packaging applications. Finally, the future development of stretchable composites based on cellulose is discussed.