A minimum functional form of the Escherichia coli BAM complex constituted by BamADE assembles outer membrane proteins in vitro.

The biogenesis of outer membrane proteins is mediated by the ß-barrel assembly machinery (BAM), which is a heteropentomeric complex composed of five proteins named BamA-E in Escherichia coli. Despite great progress in the BAM structural analysis, the molecular details of BAM-mediated processes as well as the exact function of each BAM component during OMP assembly are still not fully understood. To enable a distinguishment of the function of each BAM component, it is the aim of the present work to examine and identify the effective minimum form of the E. coli BAM complex by use of a well-defined reconstitution strategy based on a previously developed versatile assay. Our data demonstrate that BamADE is the core BAM component and constitutes a minimum functional form for OMP assembly in E. coli, which can be stimulated by BamB and BamC. While BamB and BamC have a redundant function based on the minimum form, both together seem to cooperate with each other to substitute for the function of the missing BamD or BamE. Moreover, the BamAE470K mutant also requires the function of BamD and BamE to assemble OMPs in vitro, which vice verse suggests that BamADE are the effective minimum functional form of the E. coli BAM complex.

Signal peptide replacement of Ag43 enables an efficient bacterial cell surface display of receptor-binding domain of coronavirus.

To enable an efficient bacterial cell surface display with effective protein expression and cell surface loading ability via autotransporter for potential vaccine development applications, the inner membrane protein translocation efficiency was investigated via a trial-and-error strategy by replacing the original unusual long signal peptide of E. coli Ag43 with 11 different signal peptides. The receptor-binding domain (RBD) of coronavirus was used as a neutral display substrate to optimize the expression conditions, and the results showed that signal peptides from PelB, OmpC, OmpF, and PhoA protein enhance the bacterial cell surface display efficiency of RBD. In addition, the temperature has also a significant effect on the autodisplay efficiency of RBD. Our data provide further technical basis for the biotechnological application of Ag43 as a bacterial surface display carrier system and further potential application in vaccine development.

Dynamically Encircling Exceptional Points in Different Riemann Sheets for Orbital Angular Momentum Topological Charge Conversion.

Orbital angular momentum (OAM) provides an additional degree of freedom for optical communication systems, and manipulating on-chip OAM is important in integrated photonics. However, there is no effective method to realize OAM topological charge conversion on chip. In this Letter, we propose a way to convert OAM by encircling two groups of exceptional points in different Riemann sheets. In our framework, any OAM conversion can be achieved on demand just by manipulating adiabatic and nonadiabatic evolution of modes in two on-chip waveguides. More importantly, the chiral OAM conversion is realized, which is of great significance since the path direction can determine the final topological charge order. Our Letter presents a special chiral behavior and provides a new method to manipulate OAM on the chip.

The Prognostic Value of Preoperative Naples Prognostic Score in Upper Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy.

This study aims to determine the prognostic value of preoperative Naples prognostic score (NPS) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). We conducted a retrospective study about UTUC patients at West China Hospital from January 2015 to June 2019. The X-Tile program was used to identify the optimal cutoff value of NPS. Overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were the endpoints of interest. Kaplan-Meier curves were used to estimate survival and Cox proportional hazard model was used for risk assessment. A total of 237 UTUC patients after RNU were identified and the threshold of NPS was determined to be 2. Preoperative high-NPS was associated with inferior OS (p = 0.004), CSS (p = 0.002) and PFS (p = 0.008), especially in locally advanced UTUC patients. Preoperative NPS was an independent predictor for OS (HR: 1.78; 95% CI: 1.08, 2.93), CSS (HR: 1.87; 95% CI: 1.11, 3.14) and PFS (HR: 1.60; 95% CI: 1.02, 2.50). The addition of NPS into the predictive model consisting of predictors from multivariate Cox regression resulted in better prediction performance. Preoperative NPS was a novel and reliable predictor for survival in UTUC patients after RNU, and should be further explored.

Pazopanib stimulates senescence of renal carcinoma cells through targeting nuclear factor E2-related factor 2 (Nrf2).

Renal cell carcinoma (RCC) is the most common kidney cancer with high mortality rate. Pazopanib has been approved for the treatment of RCC. However, the underlying mechanism is not clear. Here, we report a novel finding by showing that treatment with Pazopanib could promote cellular senescence of the human RCC cell line ACHN. Cells were stimulated with 5, 10, and 20 µM Pazopanib, respectively. Cellular senescence was measured using senescence-associated ß-galactosidase (SA-ß-Gal) staining. Western blot analysis and real-time polymerase chain reaction were used to measure the mRNA and protein expression of nuclear factor E2-related factor 2 (Nrf2), γH2AX, human telomerase reverse transcriptase (hTERT), telomeric repeat binding factor 2 (TERF2), p53 and plasminogen activator inhibitor (PAI). First, we found that exposure to Pazopanib reduced the cell viability of ACHN cells. Additionally, Pazopanib induced oxidative stress  by increasing the production of reactive oxygen species, reducing the levels of glutathione peroxidase, and promoting nuclear translocation of Nrf2. Interestingly, Pazopanib exposure resulted in DNA damage by increasing the expression of γH2AX. Importantly, Pazopanib increased cellular senescence and reduced telomerase activity. Pazopanib also reduced the gene expression of hTERT but increased the gene expression of TERF2. Correspondingly, we found that Pazopanib increased the expression of p53 and PAI at both the mRNA and protein levels. To elucidate the underlying mechanism, the expression of Nrf2 was knocked down by transduction with Ad- Nrf2 shRNA. Results indicate that silencing of Nrf2 in ACHN cells abolished the effects of Pazopanib in stimulating cellular senescence and reducing telomerase activity. Consistently, knockdown of Nrf2 restored the expression of p53 and PAI in ACHN cells. Based on these results, we explored a novel mechanism whereby which Pazopanib displays a cytotoxicity effect in RCC cells through promoting cellular senescence mediated by Nrf2.

Serum α-hydroxybutyrate dehydrogenase as a biomarker for predicting survival outcomes in patients with UTUC after radical nephroureterectomy.

PURPOSE: We aimed to determine the prognostic value of α-hydroxybutyrate dehydrogenase (α-HBDH) in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively enrolled the data of 544 UTUC patients at West China Hospital from May 2003 to June 2019. Cancer-specific survival (CSS) was the endpoint of interest. The optimal cutoff value of α-HBDH was identified by X-Tile program. After propensity score matching (PSM), we utilized Kaplan‒Meier curves to estimate survival and Cox proportional hazard model for risk assessment. A nomogram was built based on the results of multivariate analysis, and calibration curve, time-dependent receiver operating characteristic (ROC) curves and decision curve analysis were also performed to evaluate the predictive accuracy. RESULTS: Overall, 394 and 150 patients were divided into the α-HBDH-low group and α-HBDH -high group at the cutoff value of 158 U/L, respectively. After PSM, the two groups were well matched for all confounding factors. High α-HBDH was associated with inferior CSS (P = 0.006), and preoperative α-HBDH was an independent predictor for CSS (HR: 1.36; 95% CI:1.08, 1.80), especially in localized UTUC patients (HR: 2.04; 95% CI:1.11, 3.74). Furthermore, the nomogram based on α-HBDH achieved great predictive ability for CSS with areas under the curves of 0.800 and 0.778 for 3-year and 5-year CSS, respectively. CONCLUSION: Serum α-HBDH was a novel and reliable biomarker for predicting survival outcomes in UTUC patients after RNU but should be further explored.

Siamese Transformer-Based Building Change Detection in Remote Sensing Images.

To address the challenges of handling imprecise building boundary information and reducing false-positive outcomes during the process of detecting building changes in remote sensing images, this paper proposes a Siamese transformer architecture based on a difference module. This method introduces a layered transformer to provide global context modeling capability and multiscale features to better process building boundary information, and a difference module is used to better obtain the difference features of a building before and after a change. The difference features before and after the change are then fused, and the fused difference features are used to generate a change map, which reduces the false-positive problem to a certain extent. Experiments were conducted on two publicly available building change detection datasets, LEVIR-CD and WHU-CD. The F1 scores for LEVIR-CD and WHU-CD reached 89.58% and 84.51%, respectively. The experimental results demonstrate that when utilized for building change detection in remote sensing images, the proposed method exhibits improved robustness and detection performance. Additionally, this method serves as a valuable technical reference for the identification of building damage in remote sensing images.

Low TP53 variant allele frequency as a biomarker for anti-programmed death (ligand) 1 monotherapy in lung adenocarcinoma.

BACKGROUND: TP53 mutation heterogeneity should be considered when using TP53 as a predictive biomarker for anti-programmed death (ligand) 1 (PD-(L)1) monotherapy in lung adenocarcinoma (LUAD). However, whether TP53 variant allele frequency (VAF) should also be considered remains unknown. METHODS: Patients with LUAD from both published research and the local cohort were included to discover and validate the relationship between TP53 VAF and the efficacy of PD-(L)1 inhibitors. The Cancer Genome Atlas (TCGA) LUAD data were included for genomic, transcriptomic, and tumor microenvironment analysis. RESULTS: Among 159 patients in the discovery cohort, low TP53 VAF patients (VAF ≤ 25%) experienced significantly longer progression-free survival (PFS) than both high TP53 VAF (5.4 vs. 3.3 months; p = .021) and TP53-wild-type patients (5.4 vs. 2.5 months; p = .011). Multivariate Cox regression revealed low TP53 VAF as an independent biomarker of better efficacy. Among 50 patients in the combined validation cohort, median PFS of low TP53 VAF patients was also significantly longer than that of high TP53 VAF patients (12.0 vs. 2.1 months; p = .037). Analyzed with 469 TCGA LUAD samples, low TP53 VAF is associated with significantly higher PD-L1 expression, enrichment of gene sets related to T-cell activation, T cell-mediated immunity, and interferon-γ signaling pathways, and independently associated with more tumor-infiltrating CD8+ T cells compared with both high TP53 VAF and TP53-wild type. CONCLUSIONS: TP53 VAF should also be considered when using TP53 as a predictive biomarker. Only low TP53 VAF is independently associated with better efficacy of anti-PD-(L)1 monotherapy, which may result from higher PD-L1 expression and more tumor-infiltrating CD8+ T cells.

Enhanced sequestration of CO2 from simulated electrolytic aluminum flue gas by modified red mud.

The aluminum industry is facing severe economic and environmental problems due to increasing carbon emissions and growing stockpiles of red mud (RM). RM is a strongly alkaline, high-emission solid waste from the alumina industry with potential for CO2 sequestration. However, the effectiveness of RM carbon sequestration is poor, and the mechanism behind it is not well understood. In this study, the effect of microwave and tube furnace activation of RM on CO2 sequestration in alumina was first investigated at different temperatures. The result showed that the CO2 sequestration capacity of unmodified RM (URM) was only 14.35 mg/g at ambient temperature and pressure, and the CO2 sequestration capacity could be increased to 52.89 mg/g after high-temperature activation and modification. Besides, high-temperature activation and modification will effectively improve the carbon sequestration capacity of RM. The carbonized RM was characterized by FT-IR, SEM, XRD, laser particle size, TG-DSC, and pH measurements. In addition, the mechanism of RM capturing CO2 was also proposed, which shows that CO2 was finally sequestered in the RM as CaCO3. The change in particle size distribution and the mineral phase in the RM indicated that high-temperature activation modification positively affects the application of RM to the sequestration of CO2. This study can provide a promising technology for the low-carbon and green development of the aluminum industry, as well as achieving the waste treatment and utilization objective.

Electrosynthesis of Ionic Covalent Organic Frameworks for Charge-Selective Separation of Molecules.

Covalent organic frameworks (COFs) have emerged as potent material platforms for engineering advanced membranes to tackle challenging separation demands. However, the synthesis of COF membranes is currently hampered by suboptimal productivity and harsh synthesis conditions, especially for ionic COFs with perdurable charges. Herein, ionic COFs with charged nanochannels are electrically synthesized on conductive supports to rapidly construct composite membranes for charge-selective separations of small molecules. The intrinsic charging nature and strong charge intensity of ionic COFs are demonstrated to collectively dominate the membrane growth. Spontaneous repairing to diminish defects under the applied electric field is observed, in favor of generating well-grown COF membranes. Altering electrosynthetic conditions realizes the precise control over the membrane thickness and thus the separation ability. Electrically synthesized ionic COF membranes exhibit remarkable molecular separation performances due to their relatively ordered and charged nanochannels. With these charge-selective pathways, the membranes enable the efficient sieving of charged and neutral molecules with analogous structures. This study reveals an electrical route to synthesizing COF thin films, and showcases the great potential of ionic nanochannels in precise separation based on charge selectivity.

Attractive effects of previous form information on heading estimation from optic flow occur at perceptual stage.

When moving in the environment, optic flow and form (e.g., motion streaks) information generally appear simultaneously. Previous studies have shown that observers can estimate their heading by integrating the simultaneously presented form and optic flow information. Recent work also found that the previously seen optic flow affected the current heading estimation. The current study conducted two experiments to explore whether and how the heading estimation from optic flow was affected by the previously seen form information. We found that the current heading estimates from optic flow were biased toward the location of the focus of expansion of the previously seen form stimulus, showing an attractive effect of the previous form. Additionally, the results revealed that the attractive effect of the previous form occurred at the perceptual stage rather than postperceptual stages (e.g., working memory). Our findings suggest that our visual system can integrate dynamic optic flow and static form information across the temporal domain to estimate our heading direction.

Inhibition of Phenol from Entering into Condensed Freshwater by Activated Persulfate during Solar-Driven Seawater Desalination.

Recently, solar-driven seawater desalination has received extensive attention since it can obtain considerable freshwater by accelerating water evaporation at the air-water interface through solar evaporators. However, the high air-water interface temperature can cause volatile organic compounds (VOCs) to enter condensed freshwater and result in water quality safety risk. In this work, an antioxidative solar evaporator, which was composed of MoS2 as the photothermal material, expandable polyethylene (EPE) foam as the insulation material, polytetrafluoroethylene (PTFE) plate as the corrosion resistant material, and fiberglass membrane (FB) as the seawater delivery material, was fabricated for the first time. The activated persulfate (PS) methods, including peroxymonosulfate (PMS) and peroxodisulfate (PDS), were applied to inhibit phenol from entering condensed freshwater during desalination. The distillation concentration ratio of phenol (RD) was reduced from 76.5% to 0% with the addition of sufficient PMS or PDS, which means that there was no phenol in condensed freshwater. It was found that the Cl- is the main factor in activating PMS, while for PDS, light, and heat are the dominant. Compared with PDS, PMS can make full utilization of the light, heat, Cl- at the evaporator's surface, resulting in more effective inhibition of the phenol from entering condensed freshwater. Finally, though phenol was efficiently removed by the addition of PMS or PDS, the problem of the formation of the halogenated distillation by-products in condensed freshwater should be given more attention in the future.

Preparation of Iron Carbon Composite Material by Extracting Iron from Bauxite Residue and Its Adsorption of Heavy Metal Cd(II).

An effective method of iron extraction from bauxite residue was explored, and iron was used to prepare iron carbon composite material, which have a good adsorption effect on the heavy metal cadmium. After acid washing, acid leaching, Fe(III) reduction and ferrous oxalate decomposition, FeSO4·H2O(RM) was successfully extracted from bauxite residue, and the iron loss was only 4.35%. FexOy-BC(RM) nanocomposite materials were prepared by loading FeSO4·H2O(RM) onto walnut shell biochar (BC) (a kind of agricultural and forestry waste) by an in situ reduction and oxidation method. The results showed that the adsorption effect of FexOy-BC(RM) on Cd(II) was better than that of commercial FexOy-BC. XPS, TEM, SEM characterization analysis showed that FexOy-BC(RM) immobilized Cd(II) by adsorption, complexation, etc.to achieve a highly efficient adsorption of heavy metal Cd(II) in wastewater.

Medical Image Authentication Method Based on the Wavelet Packet and Energy Entropy.

The transmission of digital medical information is affected by data compression, noise, scaling, labeling, and other factors. At the same time, medical data may be illegally copied and maliciously tampered with without authorization. Therefore, the copyright protection and integrity authentication of medical information are worthy of attention. In this paper, based on the wavelet packet and energy entropy, a new method of medical image authentication is designed. The proposed method uses the sliding window to measure the energy of the detail information. In the time-frequency data distribution, the local details of the data are mined. The complexity of energy is quantitatively described to highlight the valuable information. Based on the energy weight, the local energy entropy is constructed and normalized. The adjusted entropy value is used as the feature vector of the authentication information. A series of experiments show that the authentication method has good robustness against shearing attacks, median filtering, contrast enhancement, brightness enhancement, salt-and-pepper noise, Gaussian noise, multiplicative noise, image rotation, scaling attacks, sharpening, JPEG compression, and other attacks.

Morphological and anatomical characteristics of exserted stigma sterility and the location and function of SlLst (Solanum lycopersicum Long styles) gene in tomato.

KEY MESSAGE: Anatomical changes in and hormone roles of the exserted stigma were investigated, and localization and functional analysis of SlLst for the exserted stigma were performed using SLAF-BSA-seq, parental resequencing and overexpression of SlLst in tomato. Tomato accession T431 produces stigmas under relatively high temperatures (> 27 °C, the average temperature in Harbin, China, in June-August), so pollen can rarely reach the stigma properly. This allows the percentage of male sterility exceed 95%, making the use of this accession practical for hybrid seed production. To investigate the mechanism underlying the exserted stigma male sterility, the morphological changes of, anatomical changes of, and comparative endogenous hormone (IAA, ABA, GA3, ZT, SA) changes in flowers during flower development of tomato accessions DL5 and T431 were measured. The location and function of genes controlling exserted stigma sterility were analyzed using super SLAF-BSA-seq, parental resequencing, comparative genomics and the overexpression of SlLst in tomato. The results showed that an increase in cell number mainly caused stigma exsertion. IAA played a major role, while ABA had an opposite effect on stigma exertion. Moreover, 26 candidate genes related to the exserted stigma were found, located on chromosome 12. The Solyc12g027610.1 (SlLst) gene was identified as the key candidate gene by functional analysis. A subcellular localization assay revealed that SlLst is targeted to the nucleus and cell membrane. Phenotypic analysis of SlLst-overexpressing tomato showed that SlLst plays a crucial role during stigma exsertion.

Identification and Functional Analysis of Tomato TPR Gene Family.

Tomato (Solanum lycopersicum) as an important vegetable grown around the world is threatened by many diseases, which seriously affects its yield. Therefore, studying the interaction between tomato and pathogenic bacteria is biologically and economically important. The TPR (Tetratricopeptide repeat) gene family is a class of genes containing TPR conserved motifs, which are widely involved in cell cycle regulation, gene expression, protein degradation and other biological processes. The functions of TPR gene in Arabidopsis and wheat plants have been well studied, but the research on TPR genes in tomato is not well studied. In this study, 26 TPR gene families were identified using bioinformatics based on tomato genome data, and they were analyzed for subcellular localization, phylogenetic evolution, conserved motifs, tissue expression, and GO (Gene Ontology) analysis. The qRT-PCR was used to detect the expression levels of each member of the tomato TPR gene family (SlTPRs) under biological stress (Botrytis cinerea) and abiotic stress such as drought and abscisic acid (ABA). The results showed that members of the tomato TPR family responded to various abiotic stresses and Botrytis cinerea stress, and the SlTPR2 and SlTPR4 genes changed significantly under different stresses. Using VIGS (Virus-induced gene silencing) technology to silence these two genes, the silenced plants showed reduced disease resistance. It was also shown that TPR4 can interact with atpA which encodes a chloroplast ATP synthase CF1 α subunit. The above results provide a theoretical basis for further exploring the molecular mechanism of TPR-mediated resistance in disease defense, and also provide a foundation for tomato disease resistance breeding.

BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma.

There is increasing evidence that bone morphogenetic proteins (BMP) are involved in the proliferation and drug tolerance of kidney cancer. However, the molecular mechanism of BMP8A in renal cell proliferation and drug tolerance is not clear. Here we showed that BMP8A was highly expressed in renal cell carcinoma, which suggests a poor prognosis of ccRCC. Promotion of cell proliferation and inhibition of apoptosis were detected by CCK-8 assay, Trypan Blue staining, flow cytometry and bioluminescence. BMP8A promoted resistance of As2 O3 by regulating Nrf2 and Wnt pathways in vitro and in vivo. Mechanistically, BMP8A enhanced phosphorylation of Nrf2, which, in turn, inhibited Keap1-mediated Nrf2 ubiquitination and, ultimately, promoted nuclear translocation and transcriptional activity of Nrf2. Nrf2 regulates the transcription of TRIM24 detected by ChIP-qPCR. BMP8A was highly expressed in ccRCC, which suggests a poor prognosis. BMP8A was expected to be an independent prognostic molecule for ccRCC. On the one hand, activated Nrf2 regulated reactive oxygen balance, and on the other hand, by regulating the transcription level of TRIM24, it was involved in the regulation of the Wnt pathway to promote the proliferation, invasion and metastasis of ccRCC and the resistance of As2 O3 . Taken together, our findings describe a regulatory axis where BMP8A promotes Nrf2 phosphorylation and activates TRIM24 to promote survival and drug resistance in ccRCC.

Topological Phase Transition in the Non-Hermitian Coupled Resonator Array.

In a two-dimensional non-Hermitian topological photonic system, the physics of topological states is complicated, which brings great challenges for clarifying the topological phase transitions and achieving precise active control. Here, we prove the topological phase transition exists in a two-dimensional parity-time-symmetric coupled-resonator optical waveguide system. We reveal the inherent condition of the appearance of topological phase transition, which is described by the analytical algebraic relation of coupling strength and the quantity of gain-loss. In this framework, the system can be switched between the topological and trivial states by pumping the site rings. This work provides a new degree of freedom to control topological states and offers a scheme for studying non-Hermitian topological photonics.

In Situ Growth of Cationic Covalent Organic Frameworks (COFs) for Mixed Matrix Membranes with Enhanced Performances.

Covalent organic frameworks (COFs) are increasingly utilized as doping agents for the design of advanced ultrafiltration mixed matrix membranes, thanks to their prominent nanoporosity and excellent polymer compatibility. However, current strategies are largely limited in the complicated postaddition of neutral COF particulates. Herein, cationic COFs, namely, TpEB, with sizes down to ∼39 nm are in situ synthesized in polyacrylonitrile (PAN) solution as crystalline fillers for the production of highly permeable TpEB-PAN ultrafiltration membranes. After the condensation of monomer pairs, the growth of cationic TpEB crystallites is restrained due to the electrostatic interaction with negatively charged PAN chains, leading to the formation of a homogeneous TpEB-incorporated casting solution. During the subsequent nonsolvent-induced phase separation process, TpEB crystallites facilitate exchange between the solvent and the nonsolvent because of their hydrophilic and nanoporous nature, accelerating the rate of phase inversion to form a highly porous membrane surface. Thus-prepared TpEB-PAN membranes deliver a tight rejection of BSA with water permeance of up to 380 L m-2 h-1 bar-1, which is 35.6% higher than that of the original PAN membranes prepared without TpEB. The TpEB-PAN membranes also exhibit enhanced operation stabilities and fouling resistances. This in situ growth strategy suggests a new avenue for the preparation of advanced mixed matrix membranes.

Promising efficacy of SHR-1210, a novel anti-programmed cell death 1 antibody, in patients with advanced gastric and gastroesophageal junction cancer in China.

BACKGROUND: The clinical response to anti-programmed cell death 1 (PD-1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported. METHODS: This study evaluated the efficacy and safety of SHR-1210, an anti-PD-1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD-L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR-1210 were also explored. RESULTS: Thirty patients with recurrent or metastatic gastric/GEJ adenocarcinoma who were refractory or intolerant to previous chemotherapy were enrolled between June 2, 2016, and June 8, 2017. Seven patients (23.3%) demonstrated objective responses, including 1 complete response. The objective response rates for patients with PD-L1-positive and PD-L1-negative tumors were 23.1% (3 of 13) and 26.7% (4 of 15), respectively (P = 1.000). Two treatment-related grade 3 or higher adverse events were reported: one was grade 3 pruritus, and the other (3.3%) was grade 5 interstitial lung disease. All 20 patients tested for the mismatch repair status had mismatch repair-proficient tumors, and the response rate was 30.0% (95% confidence interval, 11.9%-54.3%). Patients with a higher mutation load (4 of 10) tended to have better responses than those with fewer mutations (2 of 10), but the difference was not significant (P = .628). Patients with a >10% relative increase from the baseline LDH level were more likely to experience disease progression (90% [9 of 10]) than patients with a ≤10% change (40% [8 of 20]; P = .017). CONCLUSIONS: Anti-PD-1 antibody SHR-1210 shows encouraging efficacy in patients with advanced gastric/GEJ cancer in China, including mismatch repair-proficient subgroups.