Showing papers by "Jian Wang published in 2023"

Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer

Abstract: Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.

Room-temperature photosynthesis of propane from CO2 with Cu single atoms on vacancy-rich TiO2

Abstract: Abstract Photochemical conversion of CO 2 into high-value C 2+ products is difficult to achieve due to the energetic and mechanistic challenges in forming multiple C-C bonds. Herein, an efficient photocatalyst for the conversion of CO 2 into C 3 H 8 is prepared by implanting Cu single atoms on Ti 0.91 O 2 atomically-thin single layers. Cu single atoms promote the formation of neighbouring oxygen vacancies (V O s) in Ti 0.91 O 2 matrix. These oxygen vacancies modulate the electronic coupling interaction between Cu atoms and adjacent Ti atoms to form a unique Cu-Ti-V O unit in Ti 0.91 O 2 matrix. A high electron-based selectivity of 64.8% for C 3 H 8 (product-based selectivity of 32.4%), and 86.2% for total C 2+ hydrocarbons (product-based selectivity of 50.2%) are achieved. Theoretical calculations suggest that Cu-Ti-V O unit may stabilize the key *CHOCO and *CH 2 OCOCO intermediates and reduce their energy levels, tuning both C 1 -C 1 and C 1 -C 2 couplings into thermodynamically-favourable exothermal processes. Tandem catalysis mechanism and potential reaction pathway are tentatively proposed for C 3 H 8 formation, involving an overall ( 20 e − – 20 H + ) reduction and coupling of three CO 2 molecules at room temperature.

Passive Daytime Radiative Cooling of Silica Aerogels

Abstract: Silica aerogels are one of the most widely used aerogels, exhibiting excellent thermal insulation performance and ultralow density. However, owing to their plenitude of Si-O-Si bonds, they possess high infrared emissivity in the range of 8–13 µm and are potentially robust passive radiative cooling (PRC) materials. In this study, the PRC behavior of traditional silica aerogels prepared from methyltrimethoxysilane (MTMS) and dimethyldimethoxysilane (DMDMS) in outdoor environments was investigated. The silica aerogels possessed low thermal conductivity of 0.035 W/m·K and showed excellent thermal insulation performance in room environments. However, sub-ambient cooling of 12 °C was observed on a clear night and sub-ambient cooling of up to 7.5 °C was achieved in the daytime, which indicated that in these cases the silica aerogel became a robust cooling material rather than a thermal insulator owing to its high IR emissivity of 0.932 and high solar reflectance of 0.924. In summary, this study shows the PRC performance of silica aerogels, and the findings guide the utilization of silica aerogels by considering their application environments for achieving optimal thermal management behavior.

CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy

Abstract: Liver kinase B1 (LKB1) mutation is prevalent and a driver of resistance to immune checkpoint blockade (ICB) therapy for lung adenocarcinoma. Here leveraging single cell RNA sequencing data, we demonstrate that trafficking and adhesion process of activated T cells are defected in genetically engineered Kras-driven mouse model with Lkb1 conditional knockout. LKB1 mutant cancer cells result in marked suppression of intercellular adhesion molecule-1 (ICAM1). Ectopic expression of Icam1 in Lkb1-deficient tumor increases homing and activation of adoptively transferred SIINFEKL-specific CD8+ T cells, reactivates tumor-effector cell interactions and re-sensitises tumors to ICB. Further discovery proves that CDK4/6 inhibitors upregulate ICAM1 transcription by inhibiting phosphorylation of retinoblastoma protein RB in LKB1 deficient cancer cells. Finally, a tailored combination strategy using CDK4/6 inhibitors and anti-PD-1 antibodies promotes ICAM1-triggered immune response in multiple Lkb1-deficient murine models. Our findings renovate that ICAM1 on tumor cells orchestrates anti-tumor immune response, especially for adaptive immunity.

Accelerated Li + Desolvation for Diffusion Booster Enabling Low‐Temperature Sulfur Redox Kinetics via Electrocatalytic Carbon‐Grazfted‐CoP Porous Nanosheets

Abstract: Lithium–sulfur (Li–S) batteries are famous for their high energy density and low cost, but prevented by sluggish redox kinetics of sulfur species due to depressive Li ion diffusion kinetics, especially under low-temperature environment. Herein, a combined strategy of electrocatalysis and pore sieving effect is put forward to dissociate the Li+ solvation structure to stimulate the free Li+ diffusion, further improving sulfur redox reaction kinetics. As a protocol, an electrocatalytic porous diffusion-boosted nitrogen-doped carbon-grafted-CoP nanosheet is designed via forming the NCoP active structure to release more free Li+ to react with sulfur species, as fully investigated by electrochemical tests, theoretical simulations and in situ/ex situ characterizations. As a result, the cells with diffusion booster achieve desirable lifespan of 800 cycles at 2 C and excellent rate capability (775 mAh g−1 at 3 C). Impressively, in a condition of high mass loading or low-temperature environment, the cell with 5.7 mg cm−2 stabilizes an areal capacity of 3.2 mAh cm−2 and the charming capacity of 647 mAh g−1 is obtained under 0 °C after 80 cycles, demonstrating a promising route of providing more free Li ions toward practical high-energy Li–S batteries.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma

Abstract: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects.Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them.The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Bone‐Targeted Exosomes: Strategies and Applications

Abstract: As the global population ages, bone‐related diseases have increasingly become a major social problem threatening human health. Exosomes, as natural cell products, have been used to treat bone‐related diseases due to their superior biocompatibility, biological barrier penetration, and therapeutic effects. Moreover, the modified exosomes exhibit strong bone‐targeting capabilities that may improve efficacy and avoid systemic side effects, demonstrating promising translational potential. However, a review of bone‐targeted exosomes is still lacking. Thus, the recently developed exosomes for bone‐targeting applications in this review are focused. The biogenesis and bone‐targeting regulatory functions of exosomes, the constructive strategies of modified exosomes to improve bone‐targeting, and their therapeutic effects for bone‐related diseases are introduced. By summarizing developments and challenges in bone‐targeted exosomes, It is striven to shed light on the selection of exosome constructive strategies for different bone diseases and highlight their translational potential for future clinical orthopedics.

Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial.

Abstract: Importance High-grade gliomas (HGGs) constitute the most common and aggressive primary brain tumor, with 5-year survival rates of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas. The add-on efficacy of interferon alfa is unclear for the treatment of HGG. Objectives To compare the therapeutic efficacy and toxic effects of the combination of temozolomide and interferon alfa and temozolomide alone in patients with newly diagnosed HGG. Design, Setting, and Participants This multicenter, randomized, phase 3 clinical trial enrolled 199 patients with newly diagnosed HGG from May 1, 2012, to March 30, 2016, at 15 Chinese medical centers. Follow-up was completed July 31, 2021, and data were analyzed from September 13 to November 24, 2021. Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed HGG and had received no prior chemotherapy, radiotherapy, or immunotherapy for their HGG. Interventions All patients received standard radiotherapy concurrent with temozolomide. After a 4-week break, patients in the temozolomide with interferon alfa group received standard temozolomide combined with interferon alfa every 28 days. Patients in the temozolomide group received standard temozolomide. Main Outcomes and Measures The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability. Results A total of 199 patients with HGG were enrolled, with a median follow-up time of 66.0 (95% CI, 59.1-72.9) months. Seventy-nine patients (39.7%) were women and 120 (60.3%) were men, with ages ranging from 18 to 75 years and a median age of 46.9 (95% CI, 45.3-48.7) years. The median OS of patients in the temozolomide plus interferon alfa group (26.7 [95% CI, 21.6-31.7] months) was significantly longer than that in the standard group (18.8 [95% CI, 16.9-20.7] months; hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P = .005). Temozolomide plus interferon alfa also significantly improved median OS in patients with O6-methylguanine-DNA methyltransferase (MGMT) unmethylation (24.7 [95% CI, 20.5-28.8] months) compared with temozolomide (17.4 [95% CI, 14.1-20.7] months; HR, 0.57 [95% CI, 0.37-0.87]; P = .008). Seizure and influenzalike symptoms were more common in the temozolomide plus interferon alfa group, with 2 of 100 (2.0%) and 5 of 100 (5.0%) patients with grades 1 and 2 toxic effects, respectively (P = .02). Finally, results suggested that methylation level at the IFNAR1/2 promoter was a marker of sensitivity to temozolomide plus interferon alfa. Conclusions and Relevance Compared with the standard regimen, temozolomide plus interferon alfa treatment could prolong the survival time of patients with HGG, especially the MGMT promoter unmethylation variant, and the toxic effects remained tolerable. Trial Registration ClinicalTrials.gov Identifier: NCT01765088.

Ammonia–Mechanical Pretreatment of Wheat Straw for the Production of Lactic Acid and High-Quality Lignin

Abstract: In this study, wheat straw was fractionated into carbohydrates (cellulose and hemicellulose) by ammonia–mechanical pretreatment for l-lactic acid fermentation. Under optimal conditions (aqueous ammonia concentration: 19% w/w, liquid–solid ratio: 2.1:1 w/w, holding time: 4.80 h), the delignification was more than 60%. After enzymatic hydrolysis, the maximum conversions of cellulose and hemicellulose were 92.5% and 83.4% based on the pretreatment residue, respectively. The wheat straw hydrolysate was used to produce l-lactic acid with Thermoanaerobacter sp. DH-217G, which obtained a yield of 88.6% and an optical purity of 99.2%. The ammonia–mechanical pretreatment is an economical method for the production of fermentable monosaccharide, providing potential for further downstream high value-added applications.

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies—pharmacovigilance database analysis with real-world data validation

Abstract: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized.A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation.Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference.Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

Recent advances in magnetic nanocarriers for tumor treatment.

Abstract: Magnetic nanocarriers are nano-platforms that integrate multiple moieties based on magnetic nanoparticles for diagnostic and therapeutic purposes. In recent years, they have become an advanced platform for tumor treatment due to their wide application in magnetic resonance imaging (MRI), biocatalysis, magneto-thermal therapy (MHT), and photoresponsive therapy. Drugs loaded into magnetic nanocarriers can efficiently be directed to targeted areas by precisely reshaping their structural properties. Magnetic nanocarriers allow us to track the location of the therapeutic agent, continuously control the therapeutic process and eventually assess the efficacy of the treatment. They are typically used in synergistic therapeutic applications to achieve precise and effective tumor treatment. Here we review their latest applications in tumor treatment, including stimuli-responsive drug delivery, MHT, photoresponsive therapy, immunotherapy, gene therapy, and synergistic therapy. We consider reducing toxicity, improving antitumor efficacy, and the targeting accuracy of magnetic nanocarriers. The challenges of their clinical translation and prospects in cancer therapy are also discussed.

Relationship of Post-Transplant Lymphoproliferative Disorders (PTLD) Subtypes and Clinical Outcome in Pediatric Heart Transplant Recipients: A Retrospective Single Institutional Analysis/Experience of 558 Patients

Abstract: Simple Summary Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop in immunosuppressed transplant recipients. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients and sought to determine the correlation of PTLD subtypes with different characteristics. Our single institution retrospective study found that compared to older children, infant heart transplant recipients were less likely to develop PTLD. Infant heart transplant recipients who developed PTLD were diagnosed later than older children and had a lower rate of more aggressive PTLD. The overall survival of patients with more aggressive PTLD was significantly lower than patients with low-grade PTLD. Proper classification of the type of PTLD is important, as the subtypes of PTLD showed a significant correlation with the outcome. Abstract Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (>one year of age), infant recipients (

Learning to Adapt to Online Streams with Distribution Shifts

Abstract: Test-time adaptation (TTA) is a technique used to reduce distribution gaps between the training and testing sets by leveraging unlabeled test data during inference. In this work, we expand TTA to a more practical scenario, where the test data comes in the form of online streams that experience distribution shifts over time. Existing approaches face two challenges: reliance on a large test data batch from the same domain and the absence of explicitly modeling the continual distribution evolution process. To address both challenges, we propose a meta-learning approach that teaches the network to adapt to distribution-shifting online streams during meta-training. As a result, the trained model can perform continual adaptation to distribution shifts in testing, regardless of the batch size restriction, as it has learned during training. We conducted extensive experiments on benchmarking datasets for TTA, incorporating a broad range of online distribution-shifting settings. Our results showed consistent improvements over state-of-the-art methods, indicating the effectiveness of our approach. In addition, we achieved superior performance in the video segmentation task, highlighting the potential of our method for real-world applications.