A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement.

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving cognition. In this study, we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01 (a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative) that exhibits both anti-depression effects and improvements in cognition. D01 inhibits serotonin transporters (Ki = 30.1 ± 6.9 nmol/L) and M channels (IC50 = 10.1 ± 2.4 µmol/L). D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on locomotion. Intragastric administrations of D01 (20 and 40 mg/kg) can significantly shorten the immobility time in a mouse model of chronic restraint stress (CRS)-induced depression-like behavior. Additionally, D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice, but not fluoxetine. Furthermore, D01 reverses the long-term potentiation (LTP) inhibition induced by scopolamine. Taken together, our findings demonstrate that D01, a dual-target serotonin reuptake and M channel inhibitor, is highly effective in the treatment-resistant depression and cognitive deficits, thus holding potential for development as therapy of depression with cognitive deficits.

Interference-induced generation of a chirp-free short isolated attosecond pulse in the water window region with multicolor laser fields.

Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.

Incidence and prognosis of cardiac conduction system diseases in hypertension: the STEP trial.

Patients with cardiac conduction system diseases (CSD) may have increased incidence and mortality of cardiovascular events. Here we report a post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) randomized clinical trial (ClinicalTrials.gov number, NCT03015311) concerning the effect of intensive blood pressure (BP) control on the incidence of new-onset CSD and the prognostic implications of preexisting or new-onset CSD. The incidence of new-onset CSD was similar in the intensive (n = 205, 6.42%) and standard (n = 188, 5.94%) treatment arms. Participants with preexisting CSD had a higher risk for acute decompensated heart failure. Increased age, male sex and increased body mass index were independently associated with increased risk for new-onset CSD. Our results suggest that intensive BP control may not reduce the incidence of new-onset CSD compared with standard BP control.

The critical role of RAGE in severe influenza infection: A target for control of inflammatory response in the disease.

Controlling the excessive inflammatory response is one of the key ways to reduce the severity and mortality of severe influenza virus infections. RAGE is involved in inflammatory responses and acute lung injuries. Here, we investigated the role of RAGE and its potential application as a target for severe influenza treatment through serological correlation analysis for influenza patients, and treatment with the RAGE inhibitor FPS-ZM1 on A549 cells or mice with influenza A (H1N1) infection. The results showed high levels of RAGE were correlated with immunopathological injury and severity of influenza, and FPS-ZM1 treatment increased the viability of A549 cells with influenza A infection and decreased morbidity and mortality of influenza A virus infection in mice. The RAGE/NF-κb inflammatory signaling pathway is a major targeting pathway for FPS-ZM1 treatment in severe influenza. These findings provide further insights into the immune injury of severe influenza and a potential targeting candidate for the disease treatment.

Freezing Delay of a Drop Impacting on a Monolayer of Cold Grains.

We investigate a subfreezing droplet impact scenario in a low-humidity environment, where the target is a cold granular monolayer. When the undercooling degree of targets passes a threshold, such a granular layer effectively postpones the bulk freezing time of the droplet in comparison with the impact on the bare substrate underneath. In this case, the retraction of the droplet after impact reduces the contact area with the cold substrate, even though both the grains and the substrate are wettable to the liquid. We find that the significant changes in the dynamic behavior are triggered by freezing the liquid that wets the pores. Owing to the small dimension of the pores, the freezing process is rapid enough to match the dynamics over the droplet dimension. In certain circumstances, the rapid freezing may even stop liquid penetration and shed icing from the surface underneath.

Classification of anatomical morphology of cystic duct and its association with gallstone.

BACKGROUND: Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. AIM: To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. METHODS: A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. RESULTS: Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. CONCLUSION: The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

Polyamide Membranes with Tunable Surface Charge Induced by Dipole-Dipole Interaction for Selective Ion Separation.

Nanofiltration (NF) has the potential to achieve precise ion-ion separation at the subnanometer scale, which is necessary for resource recovery and a circular water economy. Fabricating NF membranes for selective ion separation is highly desirable but represents a substantial technical challenge. Dipole-dipole interaction is a mechanism of intermolecular attractions between polar molecules with a dipole moment due to uneven charge distribution, but such an interaction has not been leveraged to tune membrane structure and selectivity. Herein, we propose a novel strategy to achieve tunable surface charge of polyamide membrane by introducing polar solvent with a large dipole moment during interfacial polymerization, in which the dipole-dipole interaction with acyl chloride groups of trimesoyl chloride (TMC) can successfully intervene in the amidation reaction to alter the density of surface carboxyl groups in the polyamide selective layer. As a result, the prepared positively charged (PEI-TMC)-NH2 and negatively charged (PEI-TMC)-COOH composite membranes, which show similarly high water permeance, demonstrate highly selective separations of cations and anions in engineering applications, respectively. Our findings, for the first time, confirm that solvent-induced dipole-dipole interactions are able to alter the charge type and density of polyamide membranes and achieve tunable surface charge for selective and efficient ion separation.

Comparative efficacy of non-electric cooling techniques to reduce nutrient solution temperature for the sustainable cultivation of summer vegetables in open-air hydroponics.

The cultivation of summer vegetables in open-air nutrient film technique (NFT) hydroponics is limited due to the elevated nutrient solution temperature (NST). In this regard, non-electric evaporative-cooling techniques were explored to maintain NST in open-air NFT hydroponics. Four cooling setups were employed by wrapping polyvinyl chloride (PVC) grow pipes with one and two layers of either wet or dry jute fabrics and attaching them with coiled aluminum pipe buried inside a) wet sand-filled brick tunnels (Cooling Setup I), b) two inverted and vertically stacked earthen pots (Cooling Setup II), c) two inverted and vertically stacked earthen pots externally wrapped with wet jute fabric (Wrapped Cooling Setup II), and d) an earthen pitcher wrapped with wet jute fabric (Cooling Setup III). Wrapping grow pipes with two layers of wet jute fabric reduced NST by 5°C as compared to exposed (naked) grow pipes. The double-layer jute fabric-wrapped grow pipes produced 182% more reduction in NST in comparison to single layer-wrapped grow pipes. Additionally, the installation of Wrapped Cooling Setup II and Cooling Setup III outperformed Cooling Setup I and Cooling Setup II through NST reduction of approximately 4°C in comparison to control. Interestingly, Cooling Setup III showed its effectiveness through NST reductions of 193%, 88%, and 23% during 11 a.m.-12 p.m. as compared to Cooling Setup I, Cooling Setup II, and Wrapped Cooling Setup II, respectively. In contrast, Wrapped Cooling Setup II caused NST reductions of 168%, 191%, and 18% during 2-3 p.m. in comparison to Cooling Setup I, Cooling Setup II, and Cooling Setup III, respectively. Thus, the double-layer jute fabric-wrapped grow pipes linked with Wrapped Cooling Setup II can ensure summer vegetable cultivation in open-air NFT hydroponics as indicated by the survival of five out of 12 vegetable plants till harvest by maintaining NST between 26°C and 28°C.

Dang-Gui-Bu-Xue decoction improves wound healing in diabetic rats by the activation of Notch signaling.

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

Study on the Compatibility of SBR and Asphalt Base Based on Molecular Simulation.

In the field of highway construction, the application of styrene-butadiene rubber (SBR)-modified asphalt has gained popularity across different levels of road surfaces. A crucial aspect in ensuring the efficacy of this modification lies in the compatibility between SBR and the matrix asphalt. To address this, the current study utilizes molecular dynamics simulation as a technique. By establishing a model for the SBR-modified asphalt mixture, the research quantifies the compatibility level between the SBR modifier and the asphalt. The aim is to uncover the underlying mechanisms of compatibility between the SBR modifier and the base asphalt, ultimately contributing to the improvement of the storage stability of SBR-modified asphalt, which holds significant importance. The investigation began with the creation of models for both the base asphalt and the SBR modifier. A model for the SBR-modified asphalt blending system was then formulated based on these initial models. After undergoing geometry optimization and annealing procedures, the model attained its lowest energy state, providing a reliable basis for examining the performance of SBR-modified asphalt. The study proceeded to calculate solubility parameters and interaction energies of the system to evaluate the compatibility between the SBR modifier and the base asphalt at various temperatures. The analysis of these parameters shed light on the compatibility mechanism between the two components. Notably, it was found that at a temperature of 160 ℃, the compatibility was significantly enhanced. The findings were further corroborated through scanning electron microscope and rheological tests. The outcomes of this research offer theoretical guidance for the application of SBR-modified asphalt.

An integrated strategy for reducing anastomotic leakage in patients undergoing McKeown esophagectomy.

Objective: To describe our experience of reducing anastomotic leakage, a problem that has not been properly solved. Methods: Starting in January 2020, we began implementing our integrated strategy (application of an esophageal diameter-approximated slender gastric tube, preservation of the fibrous tissue around the residual esophagus and thyroid inferior pole anastomosis) in consecutive patients undergoing esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube. Additionally, the blood supply at the site of the anastomosis was evaluated with a near-infrared fluorescence thoracoscope after the completion of esophagogastric anastomosis in the integrated strategy group. Results: Of 570 patients who were reviewed, 119 (20.9%) underwent the integrated strategy, and 451 (79.1%) underwent the conventional strategy. The rate of anastomotic leakage was 2.5% in the integrated strategy group and 10.2% in the conventional strategy group (p = 0.008). In the integrated strategy group, the site of most of the anastomotic blood supply was the residual esophagus dominant (82.4%), followed by the gastroesophageal dual-dominant (12.6%) and the gastric tube dominant (5.0%). The reconstruction route was more likely to be orthotopic in the integrated strategy group than in the conventional strategy group (89.9% vs. 38.6%, p = 0.004). Gastric dilation was identified in 3.4% of the patients in the integrated strategy group and in 21.1% in the conventional strategy group. Conclusions: Patients who underwent our proposed integrated strategy (Zhengzhou Strategy) during McKeown esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube had a strikingly lower rate of anastomotic leakage and a relatively lower rate of postoperative complications, such as gastric tube dilation and delayed gastric emptying.

Twisted-layer boron nitride ceramic with high deformability and strength.

Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1-5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.

Clinical and Radiological Outcomes After Combined ACL and MPFL Reconstruction Versus Isolated ACL Reconstruction for ACL Injury With Patellar Instability.

BACKGROUND: An anterior cruciate ligament (ACL) injury accompanied by patellar instability (PI) is a topic that has gained orthopaedic surgeons' attention recently. Untreated PI is reportedly associated with worse clinical outcomes after isolated ACL reconstruction (ACLR) in patients after an ACL injury with PI. Nevertheless, the appropriate surgical approach and its long-term therapeutic effects in these patients remain unclear. PURPOSE: (1) To compare the clinical and radiological outcomes between isolated ACLR (iACLR) and combined ACLR and medial patellofemoral ligament reconstruction (cAMR) in patients after an ACL injury with PI and (2) to explore the correlations between these 2 procedures and clinical and radiological outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 106 patients diagnosed with an ACL injury accompanied by PI between January 2016 and April 2021 were analyzed in this study. There were 34 patients excluded because of missing postoperative radiological data. Among the remaining 72 patients, 34 patients underwent iACLR, while 38 patients underwent cAMR. Demographic characteristics, intraoperative findings, and patient-reported outcomes (Lysholm score, subjective International Knee Documentation Committee score, and Tegner activity score) were prospectively collected. Patellar alignment parameters and worsening patellofemoral osteoarthritis (PFOA) features (evaluated with the modified Whole-Organ Magnetic Resonance Imaging Score) were analyzed longitudinally on magnetic resonance imaging. The Kujala score was used to evaluate the functional recovery of the patellofemoral joint, and redislocations of the patella were prospectively recorded. Finally, multivariate logistic regression analysis was used to explore the correlations between these 2 procedures and clinical (not achieving the minimal detectable change [MDC] for the Lysholm score) and radiological (worsening PFOA features) outcomes. RESULTS: The mean follow-up duration was 28.9 ± 6.2 and 27.1 ± 6.8 months for the iACLR and cAMR groups, respectively (P = .231). Significantly higher Lysholm scores (88.3 ± 9.9 vs 82.1 ± 11.1, respectively; P = .016) and subjective International Knee Documentation Committee scores (83.6 ± 11.9 vs 78.3 ± 10.2, respectively; P = .046) were detected in the cAMR group compared with the iACLR group postoperatively. The rates of return to preinjury sports were 20.6% and 44.7% in the iACLR and cAMR groups, respectively (difference, 24.1% [95% CI, 3.3%-45.0%]; P = .030). Moreover, the rates of worsening PFOA features were 44.1% and 18.4% in the iACLR and cAMR groups, respectively (difference, 25.7% [95% CI, 4.9%-46.4%]; P = .018). In addition, significantly higher Kujala scores (87.9 ± 11.3 vs 80.1 ± 12.0, respectively; P = .006), lower redislocation rates (0.0% vs 11.8%, respectively; difference, 11.8% [95% CI, 0.9%-22.6%]; P = .045), and significantly better patellar alignment were detected in the cAMR group compared with the iACLR group postoperatively. Furthermore, multivariate logistic regression analysis determined that iACLR and partial lateral meniscectomy were significantly correlated with not achieving the MDC for the Lysholm score and worsening PFOA features in our study population. CONCLUSION: In patients after an ACL injury with PI, cAMR yielded better clinical and radiological outcomes compared with iACLR, with better patellar stability and a lower proportion of worsening PFOA features. Furthermore, not achieving the MDC for the Lysholm score and worsening PFOA features were significantly correlated with iACLR and partial lateral meniscectomy. Our study suggests that cAMR may be a more appropriate procedure for patients after an ACL injury with PI, which warrants further high-level clinical evidence.

Association of organ damage with predicted fat mass in a community-dwelling elderly: the Northern Shanghai study.

BACKGROUND: Body fat mass (FM) is associated with multiple organ damage. However, data regarding the relationship between various organ damage and FM are rare in the elderly. Therefore, we aim to perform an analysis on the relationship between organ damage and FM in a geriatric cohort. METHODS: 3331 participants were included in this analysis. Based on age, body height, body weight, waist circumference, and race, we calculated FM with the established formula. Organ damage, including arterial stiffening, lower extremity atherosclerosis, left ventricular hypertrophy (LVH), micro-albuminuria, and chronic kidney disease (CKD), were measured and calculated with standard methods. RESULTS: All organ damage parameters were significantly related to FM (all p < 0.001). In univariate logistics regression, the highest quartile of FM was tied to the increased risk of arterial stiffening, lower extremity atherosclerosis, LVH, micro-albuminuria, and CKD (all p < 0.05). After adjustment, participants with higher quantiles of FM had a significantly increased odd ratio (OR) for arterial stiffening [OR = 1.51, 95% confidence interval (CI): 1.15-1.99, p = 0.002] and LVH (OR = 1.99, 95% CI: 1.48-2.67, p < 0.001). Moreover, FM was linearly associated with arterial stiffening and LVH in total population and gender subgroups. Independent of confounders, FM was significantly correlated with arterial stiffening, lower extremity atherosclerosis, LVH and CKD in female, while was only related to LVH in male. CONCLUSIONS: Among various organ damage, elevated FM is significantly and independently associated with arterial stiffening and LVH in the elderly. Compared with men, women with increased FM are more likely to have multiple organ damage.

Relationship between physical activity and specific working memory indicators of depressive symptoms in university students.

BACKGROUND: The detection rate of depression among university students has been increasing in recent years, becoming one of the main psychological diseases that endangers their physical and mental health. According to statistics, self-harm and suicide, for which there is no effective intervention, are the second leading causes of death. AIM: To explore the relationship between different elements and levels of physical activity and college students' depression-symptom-specific working memory indicators. METHODS: Of 143 college students were analyzed using the Beck Depression Self-Rating Scale, the Physical Activity Rating Scale, and the Working Memory Task. RESULTS: There was a significant difference between college students with depressive symptoms and healthy college students in completing verbal and spatial working memory (SWM) tasks correctly (all P < 0.01). Physical Activity Scale-3 scores were significantly and positively correlated with the correct rate of the verbal working memory task (r = 0.166) and the correct rate of the SWM task (r = 0.210) (all P < 0.05). There were significant differences in the correct rates of verbal and SWM tasks according to different exercise intensities (all P < 0.05) and different exercise durations (all P < 0.05), and no significant differences in the correct rates of verbal and SWM tasks by exercise frequency (all P > 0.05). CONCLUSION: An increase in physical exercise among college students, particularly medium- and high-intensity exercise and exercise of 30 min or more, can improve the correct rate of completing working memory tasks.

Liquid lens based holographic camera for real 3D scene hologram acquisition using end-to-end physical model-driven network.

With the development of artificial intelligence, neural network provides unique opportunities for holography, such as high fidelity and dynamic calculation. How to obtain real 3D scene and generate high fidelity hologram in real time is an urgent problem. Here, we propose a liquid lens based holographic camera for real 3D scene hologram acquisition using an end-to-end physical model-driven network (EEPMD-Net). As the core component of the liquid camera, the first 10 mm large aperture electrowetting-based liquid lens is proposed by using specially fabricated solution. The design of the liquid camera ensures that the multi-layers of the real 3D scene can be obtained quickly and with great imaging performance. The EEPMD-Net takes the information of real 3D scene as the input, and uses two new structures of encoder and decoder networks to realize low-noise phase generation. By comparing the intensity information between the reconstructed image after depth fusion and the target scene, the composite loss function is constructed for phase optimization, and the high-fidelity training of hologram with true depth of the 3D scene is realized for the first time. The holographic camera achieves the high-fidelity and fast generation of the hologram of the real 3D scene, and the reconstructed experiment proves that the holographic image has the advantage of low noise. The proposed holographic camera is unique and can be used in 3D display, measurement, encryption and other fields.

The stimulus-driven and representation-driven cross-modal attentional spreading are both modulated by audiovisual temporal synchrony.

Multisensory integration and attention can interact in a way that attention to the visual constituent of a multisensory object results in an attentional spreading to its ignored auditory constituent, which can be either stimulus-driven or representation-driven depending on whether the object's visual constituent receives extra representation-based selective attention. Previous research using simple unrelated audiovisual combinations has shown that the stimulus-driven attentional spreading is contingent on audiovisual temporal simultaneity. However, little is known about whether this temporal constraint applies also to the representation-driven attentional spreading, and whether it holds for the stimulus-driven process elicited by real-life multisensory objects. The current event-related potential study investigated these questions by systematically manipulating the visual-to-auditory stimulus onset asynchrony (SOA: 0/100/300 ms) in an object-selective visual recognition task wherein the representation-driven and stimulus-driven spreading processes, measured as two distinct auditory negative difference (Nd) components, could be isolated independently. Our results showed that both the representation-driven and stimulus-driven Nds decreased as the SOA increased. Interestingly, the representation-driven Nd was completely absent, whereas the stimulus-driven Nd was still robust, when the auditory constituents were delayed by 300 ms. These findings not only indicate that the role of audiovisual simultaneity in the representation-driven attentional spreading has been underestimated, but also suggest that learned associations between the unisensory constituents of real-life objects render the stimulus-driven attentional spreading more tolerant of audiovisual asynchrony.

Targeting TIGIT for cancer immunotherapy: recent advances and future directions.

As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT. It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.

Color liquid crystal grating based color holographic 3D display system with large viewing angle.

Holographic 3D display is highly desirable for numerous applications ranging from medical treatments to military affairs. However, it is challenging to simultaneously achieve large viewing angle and high-fidelity color reconstruction due to the intractable constraints of existing technology. Here, we conceptually propose and experimentally demonstrate a simple and feasible pathway of using a well-designed color liquid crystal grating to overcome the inevitable chromatic aberration and enlarge the holographic viewing angle, thus enabling large-viewing-angle and color holographic 3D display. The use of color liquid crystal grating allows performing secondary diffraction modulation on red, green and blue reproduced images simultaneously and extending the viewing angle in the holographic 3D display system. In principle, a chromatic aberration-free hologram generation mechanism in combination with the color liquid crystal grating is proposed to pave the way for on such a superior holographic 3D display. The proposed system shows a color viewing angle of ~50.12°, which is about 7 times that of the traditional system with a single spatial light modulator. This work presents a paradigm for achieving desirable holographic 3D display, and is expected to provide a new way for the wide application of holographic display.