Strategies to enhance the therapeutic efficacy of anti-PD-1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody in cancer therapy.

Although immune checkpoint inhibitors (anti-PD-1 antibody, anti-PD-L1 antibody, and anti-CTLA-4 antibody) have displayed considerable success in the treatment of malignant tumors, the therapeutic effect is still unsatisfactory for a portion of patients. Therefore, it is imperative to develop strategies to enhance the effect of these ICIs. Increasing evidence strongly suggests that the key to this issue is to transform the tumor immune microenvironment from a state of no or low immune infiltration to a state of high immune infiltration and enhance the tumor cell-killing effect of T cells. Therefore, some combination strategies have been proposed and this review appraise a summary of 39 strategies aiming at enhancing the effectiveness of ICIs, which comprise combining 10 clinical approaches and 29 foundational research strategies. Moreover, this review improves the comprehensive understanding of combination therapy with ICIs and inspires novel ideas for tumor immunotherapy.

Highly selective and sensitive surface-enhanced Raman scattering sensors for the detection of peroxynitrite in cells.

In the physiological and pathological processes, evaluating the role of peroxynitrite (ONOO-) in living cells with high sensitivity and selectivity is a significant challenge. In this study, a highly sensitive surface-enhanced Raman spectroscopy sensor (SERS) was proposed using 3-methoxyphenylborate pinacol ester (MAPE) modified gold nanoflowers (Au NFs/MAPE) for the detection of ONOO- in living cells. The principle of the nanosensor is based on ONOO- which can oxidize aryl boric acid on Au NFs to release phenol, resulting in changes in the SERS spectrum of the sensors. The results show that the SERS sensors have high selectivity and excellent sensitivity for ONOO- in the presence of other interfering ions. The detection limit of the sensors is as low as 0.48 µM, which can meet the needs in biological systems. In addition, the SERS sensors have long-term stability and high biocompatibility. More importantly, this sensor can successfully monitor active biological samples and detect the ONOO- content generated during an oxidative stress reaction, creating a new method for studying cell biochemistry.

Satellite Interference Source Direction of Arrival (DOA) Estimation Based on Frequency Domain Covariance Matrix Reconstruction.

Direction of arrival (DOA) estimation is an effective method for detecting various active interference signals during the satellite navigation process. It can be utilized for both interference detection and anti-interference applications. This paper proposes a DOA estimation algorithm for satellite interference sources based on frequency domain covariance matrix reconstruction (FDCMR) to address various types of active interference that may occur in the satellite navigation positioning process. This algorithm can estimate the DOA of coherent signals from multiple frequency points under low signal-to-noise ratio (SNR) conditions. The signals received from the array are transformed from the time domain to the frequency domain using a fast Fourier transform (FFT). The data corresponding to the frequency point of the target signal is extracted from the signal in the frequency domain. The frequency domain covariance matrix of the received array signals is reconstructed by utilizing its covariance matrix property. The spatial spectrum search method is used for the final DOA estimation. Simulation experiments have shown that the proposed algorithm performs well in the DOA estimation under low SNR conditions and also resolves coherency. Moreover, the algorithm's effectiveness is verified through comparison with three other algorithms. Finally, the algorithm's applicability is validated through simulations of various interference scenarios.

Revealing the effect of grain boundary segregation on Li ion transport in polycrystalline anti-perovskite Li3ClO: a phase field study.

Lithium ion transport in a polycrystalline solid-state electrolyte (SSE) is directly linked to the properties of lithium ion batteries. Grain boundaries (GBs), as essential defects in SSE, have been found to play a significant role in the overall kinetics of lithium ion transport, however, the mechanism is not well understood due to the complex role of GBs. The GBs could affect the overall kinetics of ionic transport in the SSEs in two ways: (i) Li/Na diffusivities inside the GBs could be different from those in the bulk, and (ii) point defect segregation at the GBs. The first aspect is well recognized, whereas the second one has been rarely studied. In this study, a combination of first principles and phase field calculations were performed, in which the interaction between point defects and grain boundaries were considered at different scales, to reveal the role of GBs in the overall ionic conduction of SSE anti-perovskite Li3ClO. The results show that defect segregation, which varies significantly with the GB orientation, reinforces the negative contribution of GBs on the overall ionic diffusivity by approximately one-order of magnitude. This study could help improve the fundamental understanding of ionic transport in polycrystalline SSEs, and provide guidance for the design of new SSEs with excellent ionic conductivity.

Catalytic asymmetric Povarov reaction of isatin-derived 2-azadienes with 3-vinylindoles.

The first catalytic asymmetric Povarov reaction of isatin-derived 2-azadienes with 3-vinylindoles was established in the presence of chiral phosphoric acid, which tolerates a wide range of substrates with generally excellent diastereoselectivity and good enantioselectivity (up to >95 : 5 dr, 89 : 11 er). This approach will greatly enrich the chemistry of the catalytic asymmetric Povarov reaction, in particular ketone-involved transformations. Furthermore, this protocol represents the first diastereo- and enantio-selective construction of a spiro[indolin-3,2'-quinoline] framework bearing an indole moiety. This novel type of spiro-compound not only contains two chiral centers, including one quaternary stereogenic center, but also integrates two biologically important structures of spiro[indolin-3,2'-quinoline] and indole, which may find medicinal applications after bioassay.

[Orthopedic robot-assisted endoscopic transforaminal lumbar interbody fusion for lumbar disc herniation with lumbar instability].

OBJECTIVE: To explore the safety and effectiveness of the robot-assisted system for transforaminal percutaneous endoscopic in the treatment of lumbar disc herniation with lumbar instability. METHODS: From October 2021 to March 2023, 26 patients with single-segment lumbar disc herniation and lumbar spinal instability were treated with robot-assisted system for transforaminal percutaneous endoscopic. The operation time, intraoperative blood loss, incision length, postoperative drainage volume, postoperative ambulation activity time, postoperative hospitalization time were record. The intervertebral space height and the lumbar lordosis angle before and after surgery were observed and compared. Pain level was evaluated using the visual analogue scale(VAS). The clinical efficacy was evaluated by Oswestry disability index(ODI). The interbody fusion was evaluated by Brantigan Steffee criteria. RESULTS: All patients successfully completed the operation, the operation time ranged form 105 to 109 min with an average of (150.8±24.1) min. Intraoperative blood loss ranged form 35 to 88 ml with an average of (55.5±16.4) ml. Incision length ranged form 1.4 to 3.5 cm with an average of (2.3±0.8) cm. Postoperative drainage volume ranged form 15 to 40 ml with an average of (28.5±7.8) ml. Postoperative ambulation time ranged form 15 to 30 h with an average of (22.8±4.5) h. Postoperative hospitalization time was 3 to 7 d with an average of (4.2±1.3) d. Total of 26 patients were followed up, the duration ranged from 12 to 16 months with an average of (14.0±1.3) months. The VAS and ODI at 1 week [(2.96±0.72) points, (41.63±4.79)%] and 12 months[(1.27±0.60) points, (13.11±2.45)%] were significantly different from those before surgery[(6.69±0.93) points, (59.12±5.92)%], P<0.01. The height of the intervertebral space (11.95±1.47) mm and lumbar lordosis (57.46±7.59)° at 12 months were significantly different from those before surgery [(6.67±1.20) mm, (44.08±7.79)°], P<0.01. At 12 months after surgery, all patients had no pedicle screw rupture or dislocation of the fusion cage, and the intervertebral fusion was successful. According to Brantigan-Steffee classification, 17 cases were grade D and 9 cases were grade E. CONCLUSION: Robot-assisted system for transforaminal percutaneous endoscopic for the treatment of single-segment lumbar disc herniation with lumbar instability improved the accuracy and safety of the operation, and the clinical effect of early follow-up is accurate.

Simultaneous determination of furfural, acetic acid, and 5-hydroxymethylfurfural in corncob hydrolysates using liquid chromatography with ultraviolet detection.

A single-laboratory validation study was conducted using HPLC for detecting and quantifying acetic acid, furfural, and 5-hydroxymethylfurfural (HMF) in corncob hydrolysates. A pretreatment procedure using dilute sulfuric acid was optimized for corncob hydrolysis. The final hydrolysates were analyzed by HPLC using a C18 RP column with aqueous 0.01% (v/v) H2SO4-CH3OH (95 + 5) as the mobile phase at a flow rate of 1 mL/min. The wavelengths for detecting the three compounds were changed to their optimal UV detection wavelengths at the time of elution. The wavelength detection adjustments were as follow: 205 nm (0 to 4 min); 284 nm (4 to 7 min); and 276 nm (7 to 10 min). Separation was achieved with a chromatographic run time of 10 min. The calibration curves for the three compounds had correlation coefficients (r2) > or = 99.8%. The analytical range, as defined by the calibration curves, was 0.5-10 mg/L for acetic acid, 0.4-22 mg/L for furfural, and 0.1-18 mg/L for HMF. The LODs for acetic acid, furfural, and HMF were estimated to be 0.05, 0.03, and 0.02 mg/L, respectively; the LOQs were 0.196, 0.135, and 0.074 mg/L, respectively. The RSD values for the intraday precision study ranged from 0.31 to 2.22%, and from 0.57 to 2.43% for the interday study. The mean recovery rates in all compounds were between 100.08 and 101.49%.

Synergistic Transition-Metal Selenide Heterostructure as a High-Performance Cathode for Rechargeable Aluminum Batteries.

We synthesize and characterize a rechargeable aluminum battery cathode material composed of heterostructured Co3Se4/ZnSe embedded in a hollow carbon matrix. This heterostructure is synthesized from a metal-organic framework composite, in which ZIF-8 is grown on the surface of ZIF-67 cube. Both experimental and theoretical studies indicate that the internal electric field across the heterostructure interface between Co3Se4 and ZnSe promotes the fast transport of electron and Al-ion diffusion. As a result, the heterostructured Co3Se4/ZnSe demonstrates superior specific capacity and cycle stability compared to the single-phase Co3Se4 and ZnSe cathode materials.

Preoperative prediction and risk assessment of microvascular invasion in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and highly lethal tumors worldwide. Microvascular invasion (MVI) is a significant risk factor for recurrence and poor prognosis after surgical resection for HCC patients. Accurately predicting the status of MVI preoperatively is critical for clinicians to select treatment modalities and improve overall survival. However, MVI can only be diagnosed by pathological analysis of postoperative specimens. Currently, numerous indicators in serology (including liquid biopsies) and imaging have been identified to effective in predicting the occurrence of MVI, and the multi-indicator model based on deep learning greatly improves accuracy of prediction. Moreover, several genes and proteins have been identified as risk factors that are strictly associated with the occurrence of MVI. Therefore, this review evaluates various predictors and risk factors, and provides guidance for subsequent efforts to explore more accurate predictive methods and to facilitate the conversion of risk factors into reliable predictors.

Ferromagnetism induced by in-plane strain in a bulk VS2-based superlattice: (LiOH)0.1VS2.

Transition metal dichalcogenides (TMDs) have attracted intensive research interest due to their diverse properties. However, ferromagnetism is not observed in layered TMDs, except for monolayer VSe2. In this study, we report the synthesis of a bulk ferromagnetic material (LiOH)0.1VS2 based on topochemical reactions. The results demonstrate that the (LiOH)0.1VS2 crystal exhibits strong anisotropic ferromagnetism below a critical temperature of 40 K. Calculations uncover that the in-plane strains in a VS2 superlattice can induce large magnetic anisotropic energy, which stabilizes the long-range ferromagnetic order. The findings provide a new approach to induce ferromagnetism in bulk TMD materials.

High anisotropy in electrical and thermal conductivity through the design of aerogel-like superlattice (NaOH)0.5NbSe2.

Interlayer decoupling plays an essential role in realizing unprecedented properties in atomically thin materials, but it remains relatively unexplored in the bulk. It is unclear how to realize a large crystal that behaves as its monolayer counterpart by artificial manipulation. Here, we construct a superlattice consisting of alternating layers of NbSe2 and highly porous hydroxide, as a proof of principle for realizing interlayer decoupling in bulk materials. In (NaOH)0.5NbSe2, the electric decoupling is manifested by an ideal 1D insulating state along the interlayer direction. Vibration decoupling is demonstrated through the absence of interlayer models in the Raman spectrum, dominant local modes in heat capacity, low interlayer coupling energy and out-of-plane thermal conductivity (0.28 W/mK at RT) that are reduced to a few percent of NbSe2's. Consequently, a drastic enhancement of CDW transition temperature (>110 K) and Pauling-breaking 2D superconductivity is observed, suggesting that the bulk crystal behaves similarly to an exfoliated NbSe2 monolayer. Our findings provide a route to achieve intrinsic 2D properties on a large-scale without exfoliation.

Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants.

It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.

Investigations of different chemiluminescent peaks in H2O2-SCN(-)-Cu(2+)-OH(-)-luminol flow system.

In the H2O2-SCN(-) -Cu(2+)-OH(-)-luminol oscillatory system of chemiluminescence, the effects of the ingredient concentrations, temperature, flow rate and complexing agent on the oscillatory dynamics were investigated in a continuous-flow stirred tank reactor (CSTR). The dynamical structure of two peaks during a period was discussed in detail. By addition of EDTA to the oscillating system, the peak I height decreased sharply while the peak II height was little affected, and the period kept constant. This may be due to the fast reaction between Cu(II) and EDTA and the highly stable complex Cu(II)-EDTA. From the experimental study and mechanism analysis, the chemiluminescent peak I corresponds to Cu(II) → Cu(I) transformation and the peak II corresponds to the Cu(I) → Cu(II) transformation process. The key species involving in the two-transformation process are inferred to be superoxide radical and hydroxyl radical.

Thermodynamic study on the effects of beta-cyclodextrin inclusion with berberine.

The fluorescence enhancement of berberine (Berb) as a result of complex with beta-cyclodextrin (beta-CD) is investigated. The association constants of alpha-CD and beta-CD with Berb are 60 and 137 M(-1) at 20 degrees C in pH 7.20 aqueous solution. Effects of temperature on the forming inclusion complexes of beta-CD with Berb have been examined through using fluorescence titration. Enthalpy and entropy values calculated from fluorescence data are -33.7 kJ mol(-1) and 74.3 J x mol(-1) K(-1) respectively. It was found that the dielectric constant of beta-CD cavity is about 24 in a rough analogy with absolute alcohol. These results suggest that the extrusion of 'high energy water' molecules from the cavity of beta-CD and hydrophobic interaction upon the inclusion complex formation are the main forces of the inclusion reaction. Effect of pH on the association of beta-CD with Berb was also studied. Mechanism of the inclusion of beta-CD with Berb is further studied by absorption and NMR measurements. Results show that beta-CD forms a 1:1 inclusion complex with Berb.

[The interaction of berberine and human serum albumin].

The interaction of berberine and Human Serum Albumin (HSA) has been studied by fluorescence and UV-Vis absorption spectroscopy. With fluorescence quenching method, the binding constant K was found to be 1.168 x 10(5) L x mol(-1) and the number of binding site n was 5.26. The binding distance (R = 3.44 nm) and energy transfer efficiency (E = 0.303) were also obtained according to Förster's non-radiation energy transfer theory. The energy transfer path between tyrosine residual and tryptophan residual was cut by berberine in the site of HSA and weak fluorescence berberine-HSA complex was also observed.

Damage to mtDNA in liver injury of patients with extrahepatic cholestasis: the protective effects of mitochondrial transcription factor A.

Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of chronic liver cholestasis. Mitochondrial DNA (mtDNA) is highly susceptible to oxidative stress and mtDNA damage leads to mitochondrial dysfunction. This study aimed to investigate the mtDNA alterations that occurred during liver injury in patients with extrahepatic cholestasis. Along with an increase in malondialdehyde (MDA) levels and a decrease in ATP levels, extrahepatic cholestatic patients presented a significant increase in mitochondrial 8-hydroxydeoxyguanosine (8-OHdG) levels and decreases in mtDNA copy number, mtDNA transcript levels, and mtDNA nucleoid structure. In L02 cells, glycochenodeoxycholic acid (GCDCA) induced similar damage to the mtDNA and mitochondria. In line with the mtDNA alterations, the mRNA and protein levels of mitochondrial transcription factor A (TFAM) were significantly decreased both in cholestatic patients and in GCDCA-treated L02 cells. Moreover, overexpression of TFAM could efficiently attenuate the mtDNA damage induced by GCDCA in L02 cells. However, without its C-tail, ΔC-TFAM appeared less effective against the hepatotoxicity of GCDCA than the wild-type TFAM. Overall, our study demonstrates that mtDNA damage is involved in liver damage in extrahepatic cholestatic patients. The mtDNA damage is attributable to the loss of TFAM. TFAM has mtDNA-protective effects against the hepatotoxicity of bile acid during cholestasis.