Clinical outcomes and biomarker exploration of first-line PD-1 inhibitors plus chemotherapy in patients with low PD-L1-expressing of gastric or gastroesophageal junction adenocarcinoma.

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Perovskite Solar Cells Based on Polymerized Chlorophyll Films as Environmentally Friendly Hole-Transporting Layers.

Hole-transporting layers (HTLs) play a crucial role in the performance of inverted, p-i-n perovskite solar cells (PSCs). Chlorophylls (Chls) are naturally abundant organic photoconductors on earth, with good charge carrier mobility and appropriate Fermi energy levels that make them promising candidates for use in photovoltaic devices. However, Chls films prepared using the solution method exhibit lower carrier mobility compared to other organic polymer films, which limits their application in PSCs. To address this issue, Chls molecules are chemically linked to reduce the charge transfer barrier, thus the transfer of charges between molecules is transformed to intramolecular charge transfer. This study synthesizes and characterizes two polymerized Chl films, PolyCuChl and PolyNiChl, as HTLs of CH3 NH3 PbI3 -based PSCs. PSCs based on the electrochemical polymerization of PolyChl HTLs demonstrate an enhanced power conversion efficiency (PCE) of up to 19.0%, which is the highest efficiency among devices based on Chl materials. Furthermore, these devices demonstrated exceptional long-term stability. These results highlight the potential of polymerized Chl films as a viable alternative to conventional HTLs in PSCs. The approach utilizes abundant, environmentally friendly, and versatile Chl derivatives, and can be extended to develop next-generation HTL materials for improved PSC performance.

Boosting Bifunctional Catalysis by Integrating Active Faceted Intermetallic Nanocrystals and Strained Pt-Ir Functional Shells.

PtIr-based nanostructures are fascinating materials for application in bifunctional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysis. However, the fabrication of PtIr nanocatalysts with clear geometric features and structural configurations, which are crucial for enhancing the bifunctionality, remains challenging. Herein, PtCo@PtIr nanoparticles are precisely designed and fabricated with a quasi-octahedral PtCo nanocrystal as a highly atomically ordered core and an ultrathin PtIr atomic layer as a compressively strained shell. Owing to their geometric and core-shell features, the PtCo@PtIr nanoparticles deliver approximately six and eight times higher mass and specific activities, respectively, as an ORR catalyst than a commercial Pt/C catalyst. The half-wave potential of PtCo@PtIr exhibits a negligible decrease by 9 mV after 10 000 cycles, indicating extraordinary ORR durability because of the ordered arrangement of Pt and Co atoms. When evaluated using the ORR-OER dual reaction upon the introduction of Ir, PtCo@PtIr exhibits a small ORR-OER overpotential gap of 679 mV, demonstrating its great potential as a bifunctional electrocatalyst for fabricating fuel cells. The findings pave the way for designing precise intermetallic core-shell nanocrystals as highly functional catalysts.

Lead Bromide Complex in Tri-n-octylphosphine Oxide Matrix with Bright Photoluminance and Exceptional Thermoplasticity.

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials.

A novel antioxidant iron-chelating peptide from yak skin: analysis of the chelating mechanism and digestion stability in vitro.

BACKGROUND: The global prevalence of iron deficiency has posed significant public health risks. Animal-derived collagen peptides have been recognized for their potent metal ion-chelating capabilities, which can greatly enhance the bioavailability of iron. Yak skins, typically discarded during production and processing, serve as a valuable resource. Based on yak skin collagen peptide (YSP), we have developed a novel iron-chelating peptide: yak skin collagen iron-chelating peptide (YSP-Fe). RESULTS: The maximum level of iron chelation of YSP-Fe achieved was 42.72 ± 0.65 mg g-1. Structural analysis indicated that YSP-Fe was primarily formed from amino, carboxyl and carbonyl groups combined with ferrous ions. Through examination of the amino acid composition, molecular docking and peptide sequence identification, it was determined that Gly, Asp and Arg played crucial roles in the chelation of ferrous ions by YSP. Furthermore, YSP-Fe was more stable in simulated gastrointestinal digestion compared to FeSO4. CONCLUSION: YSP-Fe demonstrated dual benefits of iron supplementation and antioxidant effects. These significant findings provide a foundation for the development of novel iron supplements and the effective utilization of yak skin as a valuable resource. © 2024 Society of Chemical Industry.

Let-7a promotes periodontal bone regeneration of bone marrow mesenchymal stem cell aggregates via the Fas/FasL-autophagy pathway.

Periodontal bone regeneration using bone marrow mesenchymal stem cell (BMMSC) transplantation is a promising method; however, the method for osteogenic differentiation of BMMSCs needs to be improved. In this research, we sought to identify the roles of let-7a in the osteogenesis of BMMSCs and to provide a potential method for periodontal bone regeneration. Our previous study revealed that Fas/FasL is a target of let-7a. In this study, we demonstrated that let-7a overexpression significantly enhanced BMMSC-CAs osteogenesis both in vitro and in vivo. Mechanistically, upregulation of Fas/FasL using the rfas/rfaslg plasmid obstructed the osteogenesis of BMMSCs by inhibiting autophagy. Furthermore, we confirmed that overexpression of let-7a activated autophagy and alleviated the inhibited osteogenesis by the autophagy inhibitor 3-MA and the rfas/rfaslg plasmid of BMMSCs. In general, our findings showed that let-7a promoted the osteogenesis of BMMSCs through the Fas/FasL-autophagy pathway, suggesting that the application of let-7a in BMMSC-CAs based periodontal bone regeneration could be a promising strategy.

Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine.

The dedicator of cytokinesis 2(DOCK2) protein, an atypical guanine nucleotide exchange factor (GEFs), is a member of the DOCKA protein subfamily. DOCK2 protein deficiency is characterized by early-onset lymphopenia, recurrent infections, and lymphocyte dysfunction, which was classified as combined immune deficiency with neutrophil abnormalities as well. The only cure is hematopoietic stem cell transplantation. Here, we report two patients harboring four novel DOCK2 mutations associated with recurrent infections including live attenuated vaccine-related infections. The patient's condition was partially alleviated by symptomatic treatment or intravenous immunoglobulin. We also confirmed defects in thymic T cell output and T cell proliferation, as well as aberrant skewing of T/B cell subset TCR-Vß repertoires. In addition, we noted neutrophil defects, the weakening of actin polymerization, and BCR internalization under TCR/BCR activation. Finally, we found that the DOCK2 protein affected antibody affinity although with normal total serum immunoglobulin. The results reported herein expand the clinical phenotype, the pathogenic DOCK2 mutation database, and the immune characteristics of DOCK2-deficient patients.

The design of highly conductive and stretchable polymer conductors with low-load nanoparticles.

Highly conductive and stretchable polymer conductors fabricated from conductive fillers and stretchable polymers are urgently needed in flexible electronics, implants, soft robotics, etc. However, polymer conductors encounter the conductivity-stretchability dilemma, in which high-load fillers needed for high conductivity always result in the stiffness of materials. Herein, we propose a new design of highly conductive and stretchable polymer conductors with low-load nanoparticles (NPs). The design is achieved by the self-assembly of surface-modified NPs to efficiently form robust conductive pathways. We employ computer simulations to elucidate the self-assembly of the NPs in the polymer matrices under equilibrium and tensile states. The conductive pathways retain 100% percolation probability even though the loading of the NPs is lowered to ∼2% volume. When the tensile strain reaches 400%, the percolation probability of the ∼2% NP system is still greater than 25%. The theoretical prediction suggests a way for advancing flexible conductive materials.

Efficacy of different strategies of responsive neurostimulation on seizure control and their association with acute neurophysiological effects in rats.

Responsive neurostimulation (RNS) has shown promising but limited efficacy in the treatment of drug-resistant epilepsy. The clinical utility of RNS is hindered by the incomplete understanding of the mechanism behind its therapeutic effects. Thus, assessing the acute effects of responsive stimulation (AERS) based on intracranial EEG recordings in the temporal lobe epilepsy rat model may provide a better understanding of the potential therapeutic mechanisms underlying the antiepileptic effect of RNS. Furthermore, clarifying the correlation between AERS and seizure severity may help guide the optimization of RNS parameter settings. In this study, RNS with high (130 Hz) and low frequencies (5 Hz) was applied to the subiculum (SUB) and CA1. To quantify the changes induced by RNS, we calculated the AERS during synchronization by Granger causality and analyzed the band power ratio in the classic power band after different stimulations were delivered in the interictal and seizure onset periods, respectively. This demonstrates that only targets combined with an appropriate stimulation frequency could be efficient for seizure control. High-frequency stimulation of CA1 significantly shortened the ongoing seizure duration, which may be causally related to increased synchronization after stimulation. Both high-frequency stimulation of the CA1 and low-frequency stimulation delivered to the SUB reduced seizure frequency, and the reduced seizure risk may correlate with the change in power ratio near the theta band. It indicated that different stimulations may control seizures in diverse manners, perhaps with disparate mechanisms. More focus should be placed on understanding the correlation between seizure severity and synchronization and rhythm around theta bands to simplify the process of parameter optimization.

Impact of online learning on sense of belonging among first year clinical health students during COVID-19: student and academic perspectives.

BACKGROUND: The need to belong is a fundamental human desire that provides the basis for relationships and community; it provides a sense of security that enables growth and development. This sense of belonging is pivotal to new University students, indeed, without it, students are at greater risk of failing or withdrawing from their studies. Yet developing a sense of belonging within a new cohort is complex and multi-faceted and further complicated by a sudden shift away from in-person to online learning. Using the situated-learning framework, our study explores first year clinical health students' sense of belonging in the context of the rapid transition to online learning because of the COVID-19 pandemic. METHODS: We utilised a current mixed-method approach including a survey incorporating previously validated tools, demographic and open-ended qualitative questions. Data was also gathered from three focus groups: two dedicated student groups and one academic focus group. Qualitative data was subjected to thematic analysis whilst descriptive statistics were used to describe the quantitative data. RESULTS: 179 first year students complete the survey and four students, and five academics were involved in the focus groups. All participants were from clinical health science courses at an Australian university. Our qualitative results indicated a global theme of: Navigating belonging during the COVID-19 crisis: a shared responsibility; with four organising themes describing (1) dimensions of belonging, (2) individual experiences and challenges, (3) reconceptualising teaching and learning, and (4) relationships are central to belonging. CONCLUSION: While the rapid transition to online learning did not greatly impact knowledge acquisition of first-year students in this cohort, the lack of sense of belonging highlights the need for further research into development of this essential aspect of learning in the online domain. Although contextualised in the COVID-19 pandemic, it became clear that the findings will remain relevant beyond the current situation, as a student's need to belong will always be present in the face of challenges or change.

Traffic Vibration Signal Analysis of DAS Fiber Optic Cables with Different Coupling Based on an Improved Wavelet Thresholding Method.

Distributed Acoustic Sensing (DAS) is a novel technology that uses fiber optics to sense and monitor vibrations. It has demonstrated immense potential for various applications, including seismology research, traffic vibration detection, structural health inspection, and lifeline engineering. DAS technology transforms long sections of fiber optic cables into a high-density array of vibration sensors, providing exceptional spatial and temporal resolution for real-time monitoring of vibrations. Obtaining high-quality vibration data using DAS requires a robust coupling between the fiber optic cable and the ground layer. The study utilized the DAS system to detect vibration signals generated by vehicles operating on the campus road of Beijing Jiaotong University. Three distinct deployment methods were employed: the uncoupled fiber on the road, the underground communication fiber optic cable ducts, and the cement-bonded fixed fiber optic cable on the road shoulder, and compared for their outcomes. Vehicle vibration signals under the three deployment methods were analyzed using an improved wavelet threshold algorithm, which was verified to be effective. The results indicate that for practical applications, the most effective deployment method is the cement-bonded fixed fiber optic cable on the road shoulder, followed by the uncoupled fiber on the road, and the underground communication fiber optic cable ducts are the least effective. This has important implications for the future development of DAS as a tool for various fields.

[Analysis of screening results for genetic metabolic diseases among 352 449 newborns from Changsha].

OBJECTIVE: To retrospectively analyze the screening results for genetic metabolic diseases among newborns from Changsha in order to determine the prevalence of single diseases and their mutational spectrum. METHODS: 352 449 neonates born from January 2016 to December 2021 in Changsha were subjected to tandem mass spectrometry. Suspected cases were further analyzed by biochemical and genetic testing. RESULTS: Among the 352 449 newborns, 6 170 were positive for the screening, which yielded a positive rate of 1.75%. 5 437 cases were recalled, and 92 were confirmed, with the overall prevalence being 1∶3 831 and positive predictive value of 1.69%. Eighteen genetic metabolic diseases were detected among the 92 children, including 33 amino acid metabolic disorders, among which 20 were phenylalanine hydroxylase deficiency (60.60%). 17 cases had organic acid metabolic disorders, among which 4 were 2-methyl-dehydrogenase deficiency (23.50%). 42 had fatty acid metabolic disorders, among which 27 (64.30%) were primary carnitine deficiency and 12 were short-chain acyl-CoA dehydrogenase deficiency (28.60%). In total 90 genetic variants were identified, with the most common ones including c.51C>G, c.1400C>G, c.760C>T, c.1031A>G and c.1165A>G. CONCLUSION: The common neonatal genetic metabolic diseases in Changsha include primary carnitine deficiency, phenylalanine hydroxylase deficiency and short-chain acyl-CoA dehydrogenase deficiency. The preliminary delineation of mutational spectrum for genetic metabolic diseases in Changsha can facilitate early diagnosis and intervention, so as to improve the quality of newborn population.

The thermal resistance and targeting release of zein-sodium alginate binary complexes as a vehicle for the oral delivery of riboflavin.

Riboflavin (RF) is one kind of vitamin B, which has low bioavailability due to the low water solubility and the high photosensitivity during food processing and storage. The anti-solvent precipitation method was applied to fabricate a zein-sodium alginate (SA) binary complexes delivery system with the loading of RF, which was aimed to enhance the delivery efficiency, stability, and controlled release of RF in the gastrointestinal (GI) tract. The formation mechanism, physicochemical properties as well as the digestion behaviors were investigated. The incorporation of SA significantly increased the diameter and decreased the surface positive charge of the nanoparticles. The surface morphology of the nanoparticles was characterized using the scanning electron microscope. The FTIR analysis revealed that the electrostatic attraction was the dominant binding force in the formation of the zein-SA binary complexes nanoparticles. In addition, the study on the in vitro release process showed that the zein-SA nanoparticles could delay the release of the RF under the simulated GI tract conditions, which improved their oral bioavailability. In summary, the zein-SA nanoparticle is an effective vehicle for the oral delivery of RF as well as other vitamins and bioactives in the applications of food and nutrition.

Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.

Colon cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2-like kinase 1(CLK1), CLK2, and A-kinase anchor protein 8-like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low-risk group, and TME-related pathway gene expression was also higher in low-risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.

High AKAP8L expression predicts poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a severe disease with high mortality, and is associated with poor prognosis and frequent lymphatic metastasis. Therefore, prognostic indicators for ESCC are urgently needed. A-kinase anchor-protein 8-like (AKAP8L) is a member of the A kinase anchor-protein (AKAPs) family and is overexpressed in many cancers. However, the role of AKAP8L in ESCC remains unclear. The aim of this study is to investigate the expression patterns and prognostic value of AKAP8L in ESCC. METHODS: The mRNA expression of AKAP8L was analyzed from the dataset of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry was applied to detect the AKAP8L expression in tissue microarray. Pearson's chi-square test was carried out for the correlation analysis of clinicopathological features and AKAP8L expression. The prognostic significance of clinicopathological features and AKAP8L expression was determined by univariate and multivariate Cox hazard models. Kaplan-Meier survival curve was used for survival analysis. RESULTS: We found that the mRNA level of AKAP8L was higher in tumor tissues than in adjacent tissues in TCGA and GEO dataset. High AKAP8L expression was associated with poor overall survival (OS) in ESCC patients (p = 0.0039). Besides, AKAP8L expression was highly expressed in patients with lymph node metastasis detected by ESCC tissue microarray (p = 0.0014). The comparison of the different clinicopathological features of ESCC between high and low AKAP8L expression groups revealed that high AKAP8L expression was related to lymph node stage (p = 0.041). Kaplan-Meier survival analysis revealed that high AKAP8L expression indicates an unfavorable progression-free survival (PFS) and OS in ESCC patients (p < 0.0001). Univariate and multivariate analyses confirmed that AKAP8L was an independent prognostic factor for PFS and OS in ESCC (p = 0.003 and p < 0.0001). CONCLUSIONS: In conclusion, this study demonstrated that high expression of AKAP8L is associated with poor prognosis of ESCC and can be considered an independent risk factor for ESCC.

Cu3 (HHTP)2 c-MOF/ZnO Ultrafast Ultraviolet Photodetector for Wearable Optoelectronics.

Two-dimensional conductive metal-organic frameworks (2D c-MOFs) are a family of highly tunable and electrically conducting materials that can be utilized in optoelectronics. A major issue of 2D c-MOFs for photodetection is their poor charge separation and recombination dynamics upon illumination. This study demonstrates a Cu3 (HHTP)2 /ZnO type-II heterojunction ultraviolet (UV) photodetector fabricated by layer-by-layer (LbL) deposition, in which the charge separation of photogenerated carriers is enhanced. At optimized MOF layer cycles, the device achieves a responsivity of 78.2 A/W and detectivity of 3.8×109 Jones at 1 V. Particularly, the device can be operated in the self-powered mode with an ultrafast response time of 70 µs, which is the record value for MOF-based photodetectors. In addition, even after 1000-time bending of 180°, the flexible device maintains stable performance. This flexible MOF-based UV photodetector with anti-fatigue and anti-bending properties provides strong implication to wearable optoelectronics.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer.

BACKGROUND: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. METHODS: Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 and 2-3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. RESULT: One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. TRG 2-3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001). CONCLUSION: TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP.

BACKGROUND: Premature ovarian failure (POF) is one of the common disorders found in women leading to 1% female infertility. Clinical features of POF are hypoestrogenism or estrogen deficiency. With the development of regenerative medicine, human mesenchymal stem cells (hMSCs) therapy brings new prospects for POF. This research aims to reveal the therapeutic effects and potential mechanisms of human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes on POF. METHODS: The mRNA and protein expressions in hucMSCs and ovarian granulosa cells (KGN and SVOG cells) were assessed using qRT-PCR and western blot. ELISA assay was performed to evaluate estradiol (E2) secretion in granulosa cells. The binding relationship between miR-21 and LATS1 was verified by dual-luciferase reporter assay and RNA binding protein immunoprecipitation assay (RIP) assay. Additionally, Immunoprecipitation assay was carried out to confirm Lysyl oxidase like 2 (LOXL2) was phosphorylated by large tumor suppressor 1 (LATS1). Finally, the binding relationships between Yes-associated protein (YAP), StAR and LOXL2 were verified by dual-luciferase reporter assay and/or chromatin immunoprecipitation assay (ChIP) assay. RESULTS: Here our results displayed that miR-21 was overexpressed in hucMSCs and hucMSCs-derived exosomes, compared with that ovarian granulosa cells. hucMSC-exo with overexpressing miR-21 could markedly promote the secretion of estrogen in ovarian granulosa cells. LATS1 overexpression in ovarian granulosa cells reduced the secretion of estrogen. We subsequently confirmed that LATS1 was the target of miR-21. In addition, LATS1 could regulate StAR expression by phosphorylating LOXL2 and YAP. CONCLUSION: miR-21 carried by hucMSCs-derived exosomes could downregulate LATS1, thereby reducing phosphorylated LOXL2 and YAP, and ultimately promoting estrogen secretion in ovarian granulosa cells.

Simulation and misalignment analysis of the gain ratio of a polarization Mie Raman lidar.

The gain ratio is a critical parameter in a polarization Mie lidar. Calibrating the gain ratio is essential in aerosol classification studies. We developed a ray-tracing-based simulation method to investigate the impact of mounting errors on the gain ratio. In this method, a computational model for each element of the lidar was built, and Zemax was used to simulate the lidar receiver to obtain the optical gain ratio by theoretical calculations. This method can analyze the influence of each element's mounting errors and offer a theoretical foundation for the machining and mounting accuracy of the lidar design. The correctness of the model was verified by applying it to a single-wavelength polarization Mie Raman lidar.