Research Progress in Microporous Materials for Selective Adsorption and Separation of Methane from Low-Grade Gas.

Given that methane (CH4) and nitrogen (N2) have similar properties, achieving high-purity enrichment of CH4 from nitrogen-rich low-grade gas is extremely challenging and is of great significance for sustainable development in energy and the environment. This paper reviews the research progress on carbon-based materials, zeolites, and MOFs as adsorbent materials for CH4/N2 separation. It focuses on the relationship between the composition, pore size, surface chemistry of the adsorbents, CH4/N2 selectivity, and CH4 adsorption capacity. The paper also highlights that controlling pore size and atomic-scale composition and optimizing these features for the best match are key directions for the development of new adsorbents. Additionally, it points out that MOFs, which combine the advantages of carbon-based adsorbents and zeolites, are likely to become the most promising adsorbent materials for efficient CH4/N2 separation.

Spatial Metabolomics Profiling Reveals Curcumin Induces Metabolic Reprogramming in Three-Dimensional Tumor Spheroids.

Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.

Sintilimab plus GemOx is an effective salvage therapy in patients with refractory/relapsing nodal peripheral T cell lymphomas.

PURPOSE: The retrospective study was to explore the effectiveness and safety of GemOx (gemcitabine, oxaliplatin) plus sintilimab (belongs to the class of drugs known as immune checkpoint inhibitors, particularly targeting the PD-1 receptor) in relapse or refractory nodal PTCLs. METHODS: Patients with nodal PTCL who initiated salvage therapy with sintilimab and GemOx between January 2020 to September 2021 were identified from the database of the hematology department of the Second Affiliated Hospital of Zhejiang University School of Medicine. All patients received 2-4 cycles (3 weeks/cycle) of treatment of sintilimab (200 mg, I.V, D1) in combination with GemOx. Treatment response was assessed every six weeks during the salvage treatment phase. Eligible patients received maintenance therapy according to the investigator's decision. Follow-ups were routinely conducted every three months. RESULTS: 31 patients with r/r nodal PTCLs were enrolled, including 23 PTCL-NOS, 4 AITL, and 4 ALCL. 21 (67.7%) patients received at least two lines of therapy. 71.0% (95% CI, 53.4%-83.9%) of patients documented objective response of 2-4 cycles of sintilimab plus GemOx therapy, including 9 complete response and 13 partial response. 21 (67.7%) patients received consolidation therapy, including 5 autologous stem-cell transplantation and 12 histone deacetylase inhibitors. After a median 25.6 months follow-up, the median PFS was 22.0 (95% CI,11.8-24.7) months, and the median OS was 26.2 (95% CI, 24.4 -NA) months. 29 (93.5%) patients experienced at least one adverse event, and 26 (83.9% patients only had mild (grade 1-2) AEs.Univariable Cox regression showed the progression risk of AITL is 22.7 (3.9- 131.0, p < 0.01) times of PTCL-NOS, while the HR of ALCL was 1.14 (0.33-3.96,p = 0.833). CONCLUSION: Sintilimab plus GemOx showed encouraging activity and manageable toxicity for patients with r/r PTCL.

Clinical diagnostic model for predicting indolent or aggressive lymphoma based on clinical information and ultrasound features of superficial lymph nodes.

PURPOSE: The aim of this study was to develop a diagnostic model for predicting indolent lymphoma or aggressive lymphoma using clinical information and ultrasound characteristics of superficial lymph nodes. METHOD: Patients with confirmed pathological lymphoma subtypes who had undergone ultrasound and contrast-enhanced ultrasound examinations were enrolled. Clinical and ultrasound imaging features were retrospectively analysed and compared to the pathological results, which were considered the gold standard for diagnosis. Two diagnostic models were developed: a clinical model (Model-C) using clinical data only, and a combined model (Model-US) integrating ultrasound features into the clinical model. The efficacy of these models in differentiating between indolent and aggressive lymphoma was compared. RESULTS: In total, 236 consecutive patients were enrolled, including 78 patients with indolent lymphomas and 158 patients with aggressive lymphomas. Receiver operating characteristic (ROC) curve analysis revealed that the areas under the curves of Model-C and Model-US were 0.78 (95 % confidence interval: 0.72-0.84) and 0.87 (95 % confidence interval: 0.82-0.92), respectively (p < 0.001). Model-US was further evaluated for calibration and is presented as a nomogram. CONCLUSIONS: The diagnostic model incorporated clinical and ultrasound characteristics and offered a noninvasive method for assessing lymphoma with good discrimination and calibration.

Discriminative analysis of aroma profiles in diverse cigar products varieties through integrated sensory evaluation, GC-IMS and E-nose.

Cigars, treasured for their rich aromatic profiles, occupy a notable segment in the global consumer market. The objective of this study was to characterize the volatile aroma compounds that shape the flavor profiles of six distinct varieties of Great Wall cigars, contributing to the understanding of cigar aroma analysis. Utilizing HS-GC-IMS and sensory evaluation, the study discerned the aroma profiles of GJ No. 6 (GJ), Animal from the Chinese zodiac (SX), Range Rover No. 3 Classic (JD), Miracle 132 (QJ), Sheng Shi No. 5 (SS), and Red 132 (HS) cigars. The analysis uncovered a spectrum of characteristic aromas, including tobacco, creaminess, cocoa, leather, baking, herbaceous, leathery, woodsy, and fruity notes. A total of 88 compounds were identified, categorized into 11 chemical classes, with their quantities varying among the cigars in a descending order of QJ, JD, GJ, SS, HS, and SX. 24 compounds, such as 2-heptanone, n-butanol, 2,6-dimethylpyrazine and 2-furfuryl methyl sulfide were considered as key differential components. The volatile components were effectively differentiated using principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and cluster analysis, revealing correlations between sensory attributes, key components, and electronic nose (E-nose). This research introduces a novel method for analyzing volatile aroma components in cigars, offering insights to enhance cigar quality and to foster the development of new products with unique aroma profiles.

Practice patterns in utilization of atherectomy and embolic protection devices in inpatient and outpatient treatment settings.

OBJECTIVE: The frequency of atherectomy in lower extremity arterial disease has increased substantially over the past several years, specifically in the office-based laboratory (OBL) setting, yet the efficacy compared with other interventions and the consequences of distal embolization remain unknown. Embolic protection devices (EPDs) have been used at varying rates depending on physician and practice setting. Previous studies have described lesion characteristics to consider when weighing the benefits and drawbacks associated with device use. Our study focuses on the use of atherectomy and EPDs in femoropopliteal arterial disease to better characterize resource use trends and postoperative outcomes in the inpatient and OBL interventional settings. METHODS: We conducted a retrospective analysis on endovascular interventions performed for femoral-popliteal occlusive disease that were entered into the Vascular Quality Initiative data registry between 2017 and 2021. A one:one greedy match, adjusted analysis based on inpatient or OBL location of procedure was used to compare the groups. Hierarchical logistical regression with selective use of principal component analysis was used to further explore the differences in EPD use and immediate postoperative outcomes. A proportional hazard model was used to demonstrate differences in reintervention rates up to 2 years postoperatively between patients who underwent atherectomy in the inpatient vs OBL treatment setting. RESULTS: 2849 matched pairs were inlcuded in the final analysis. In our cohort, there was 22% EPD use overall, 40% in the hospital setting and 4.4% in the OBL setting (P < .001). Among the patients with available follow-up information, OBL intervention setting increased probability of reintervention by 18% at 2 years postoperatively compared with the inpatient setting; however, there was no difference associated with EPD placement and rate of reintervention. CONCLUSIONS: Use of EPDs in the OBL setting compared with the hospital setting is dramatically decreased; however, no increased incidence of postoperative complications was seen compared to procedures performed in the hospital setting when controlling for patient and lesion characteristics. Patients with available follow-up data were more likely to undergo ipsilateral reintervention between 6 months and 2 years postoperatively if atherectomy was done in the OBL setting. Dedicated studies are encouraged to ensure patient safety, effective resource allocation, and long-term efficacy of OBL atherectomy as an ever-growing number of peripheral arterial procedures are transitioned to the OBL setting.

Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal 18F-Labeled PET Probes Specifically Targeting Estrogen Receptor α.

The estrogen receptor α positive (ERα+) subtype represents nearly 70% of all breast cancers (BCs), which seriously threaten women's health. Positron emission computed tomography (PET) characterizes its superiority in detecting the recurrence and metastasis of BC. In this article, an array of novel PET probes ([18F]R-1, [18F]R-2, [18F]R-3, and [18F]R-4) targeting ERα based on the tetrahydropyridinyl indole scaffold were developed. Among them, [18F]R-3 and [18F]R-4 showed good target specificity toward ERα and could distinguish MCF-7 (ERα+) and MDA-MB-231 (ERα-) tumors efficiently. Especially, [18F]R-3 could differentiate the ERα positive/negative tumors successfully with a higher tumor-to-muscle uptake ratio (T/M) than that of [18F]R-4. The radioactivity of [18F]R-3 in the MCF-7 tumor was 5.24 ± 0.84%ID/mL and its T/M ratio was 2.49 ± 0.62 at 25 min postinjection, which might be the optimal imaging time point in PET scanning. On the contrary, [18F]R-3 did not accumulate in the MDA-MB-231 tumor at all. The autoradiography analysis of [18F]R-3 on the MCF-7 tumor-bearing mice model was consistent with the PET imaging results. [18F]R-3 exhibited the pharmacokinetic property of rapid distribution and slow clearance, making it suitable for use as a diagnostic PET probe. Overall, [18F]R-3 was capable of serving as a PET radiotracer to delineate the ERα+ tumor and was worthy of further exploitation.

Cognitive impairment and neurocognitive profiles among people living with HIV and HIV-negative individuals older over 50 years: a comparison of IHDS, MMSE and MoCA.

We aimed to examine the l differences in the assessment of neurocognitive impairment (NCI) using cognitive screening tools between PLWH and HIV-negative individuals and further compare the neurocognitive profiles between the two groups. This was baseline evaluation of Pudong HIV Aging Cohort, including 465 people living with HIV (PLWH) and 465 HIV-negative individuals aged over 50 years matched by age (± 3 years), sex and education. NCI was assessed using the Chinese version of Mini-mental State Examination (MMSE), the International HIV Dementia Scale (IHDS) and Beijing version of Montreal Cognitive Assessment (MoCA). In total, 258 (55.5%), 91 (19.6%), 273 (58.7%) of PLWH were classified as having NCI by the IHDS, MMSE and MoCA, compared to 90 (19.4%), 25 (5.4%), 135 (29.0%) of HIV-negative individuals, respectively (p < 0.05); such associations remained significant in multivariable analysis. PLWH showed a larger overlap of NCI detected by IHDS, MMSE, and MoCA. IHDS and MoCA detected almost all of the NCI detected by MMSE. IHDS-motor and psychomotor speeds and MoCA-executive function showed the greatest disparities between two groups. In multivariable analysis, older age and more depressive symptoms were positively associated with NCI regardless of the screening tools or HIV serostatus. PLWH over 50 years old display a higher prevalence of NCI and distinct neurocognitive profiles compared to HIV-negative individuals, despite viral suppression. Given the more considerable overlap in NCI classification in PLWH, it is advisable to choose one screening tool such as IHDS or MoCA to identify those potentially having NCI and then refer to more comprehensive neuropsychological assessment.

Association between Asian race and perioperative outcomes after carotid revascularization varies with Asian procedure density.

OBJECTIVE: Postoperative outcomes following carotid revascularization are understudied in Asian patients. We aimed to assess whether disease severity and postoperative outcomes following carotid revascularization differ between Asian and White patients, and whether this varies with Asian procedure density. METHODS: We analyzed the Vascular Quality Initiative Carotid Endarterectomy and Carotid Artery Stenting datasets from 2003 to 2021. Regions were divided into tertiles based on Asian procedure density. Propensity scores were used to match Asian and White patients based on patient factors and procedure type. The primary outcome variable was a collapsed composite of in-hospital ipsilateral stroke/death/myocardial infarction. χ2 tests were used to assess association between Asian race and disease severity, center and surgeon volume, and 1-year outcomes. Logistic and Cox regressions were performed between the matched cohorts. RESULTS: A total of 1766 Asian and 159,608 White patients underwent carotid revascularization, and we identified 2704 patients (1352 Asian and 1352 White) in the matched cohorts. Among propensity matched patients, all-comer Asian patients more commonly had >80% ipsilateral stenosis (63% vs 52%; P < .001) and a moderate/severe preoperative Rankin score (7.6% vs 5.1%; P = .007). The rate of in-hospital stroke/death/myocardial infarction was higher in Asian patients (2.6% vs 1.3%; P = .012), and this disparity was more pronounced in the lowest tertile of Asian procedure density (4.3% vs 0.5%; P < .001). Logistic regression in the propensity-matched cohort demonstrated Asian race was associated with lower odds of intervention at highest volume centers (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2-0.3; P < .001) and by highest volume surgeons (OR, 0.3; 95% CI, 0.3-0.4; P < .001). Asian race was associated with higher odds of in-hospital stroke/death/myocardial infarction (OR, 2.0; 95% CI, 1.1-3.8; P = .031), and there was a significant interaction between Asian procedure density and the relationship between Asian race and this outcome (interaction P = .001). After accounting for center and surgeon volume, the association of Asian race and the composite outcome was mitigated (OR, 1.5; 95% CI, 0.7-3.3; P = .300). Cox regression between the matched cohorts demonstrated that Asian race was associated with lower 1-year mortality (hazard ratio, 0.5; 95% CI, 0.3-0.7; P = .001) and higher risk of 1-year reintervention (hazard ratio, 16; 95% CI, 1.8-142; P = .013). CONCLUSIONS: Asian patients are more likely to present with a higher degree of carotid stenosis, higher preoperative risk, and experience worse perioperative outcomes. The association of Asian race with perioperative stroke/death/myocardial infarction varies with Asian procedure density and is also confounded by center and surgeon volume. These results highlight the importance of understanding referral patterns and cultural effects on outcomes disparities in Asian patients.

CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study.

Background: Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Methods: Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0-1. We evaluated four dose levels (DL) of RJMty19 in a 3 + 3 dose-escalation scheme: 1 × 106, 3 × 106, 9 × 106 and 2 × 107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. Findings: A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N = 12, 100%), leukopenia (N = 12, 100%), lymphopenia (N = 10, 83%), thrombocytopenia (N = 6, 50%), febrile neutropenia (N = 3, 25%), and anemia (N = 3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N = 12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N = 1; DCR: 33%, N = 2). However, all DL3 patients achieved disease control (N = 3, 100%), and all DL4 patients achieved objective response (N = 3, 100%). Interpretation: Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Funding: Wyze Biotech. Co., Ltd.

Lung-Mimetic Hydrofoam Sealant to Treat Pulmonary Air Leak.

Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated. This "lung-mimetic" sealant is a hydrofoam material that has alveolar-like porous ultrastructure, lung-like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix-derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung-mimetic sealant shows minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulate key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, this lung-mimetic sealant rapidly seals air leak and restores baseline lung mechanics. Altogether, these data indicate that the lung-mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro.

Capillary-Assisted Assembly of Soft Conductive Polymer Nanopillar/Tube Arrays and Applications.

Nanopillar/tube arrays have emerged as encouraging platforms, possessing remarkable advantages, including large specific areas and highly aligned orientations. Despite the progress of nano/microfabrication technologies, facile and controllable fabrication of conductive polymer nanopillar/tube arrays remains challenging. In this study, we demonstrate that the air-liquid interfacial self-assembly can be extended to obtain three-dimensional nanostructured arrays. A smart and novel method is proposed for preparing uniform conductive polymer nanopillar/tube arrays by a template-mediated interfacial synthesis approach. By utilizing capillary force, precise control processes of the nanostructure and patterned structure can be easily realized. Furthermore, a transfer strategy is devised, allowing for scalable fabrication and expansion of the applicability. Applications, including antibacterial surfaces and actuators, have been demonstrated. We extend the air-liquid interfacial synthesis technique as a powerful and universal strategy for producing ordered nanopillar/tube arrays and show the great potential of soft nanostructured arrays as advanced platforms in diverse applications.

Recovery of extracorporeal lungs using cross-circulation with injured recipient swine.

OBJECTIVE: Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia. METHODS: Swine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation. RESULTS: Recipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours. CONCLUSIONS: We demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application.

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-ß signaling.

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor ß (TGF-ß)-Smad3 signaling with TGF-ß inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-ß inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

Chiral Nanomaterials for Cancer Vaccines.

Chirality is a fundamental characteristic of living organisms and is commonly observed at the biomolecule, cellular, and tissue levels. Chiral nanomaterials play an irreplaceable role in nanomedicine and nanobiology because of their unique enantioselectivity with biological components. Here, research progress relating to chiral nanomaterials in the field of vaccines is reviewed, including antigen presenting systems, immune adjuvants, and cancer vaccines. First, the common synthesis methods are outlined for different types of chiral nanomaterials, as well as their chiral sources, optical properties, and potential biological applications. Then, the application of chiral nanomaterials are discussed in the field of vaccines with reference to the promotion of antigen presentation and activation of the immune system for tumor immunotherapy. Finally, the current obstacles and future research directions of chiral nanomaterials are revealed with regard to regulating the immune system.

Outcomes and risk factors of SARS-CoV-2 omicron variant in B-cell lymphoma patients following CD19 targeted CAR-T therapy.

BACKGROUND: Little was known on infection and mortality rates, still less the risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant in B-cell lymphoma patients following CD19 targeted chimeric antigen receptor T cell (CAR-T). AIMS: We performed a retrospective multicenter study and analyzed the details of relapsed/refractory (R/R) B-cell lymphoma patients who received CD19 targeted CAR-T heretofore in five cellular immunotherapy centers in China during the omicron wave. MATERIALS & METHODS: One hundred fifty-four patients were enrolled in this study. RESULTS: Among them, 52 patients (33.8%) were uninfected, 74 patients (48.1) had ambulatory mild disease (including nine patients of asymptomatic infection), 22 patients (14.3%) had moderate disease and six patients (3.9%) had severe disease when data collected up. Three patients with severe disease died from COVID-19, the death rate was 1.9% for all enrolled patients, and 2.9% for infected patients. We also found that patients over 60 years old or with diabetes mellitus (DM) tend to develop severe disease (p = 0.0057 and p = 0.0497, respectively). Patients had CAR-T infusion within 6 months also tend to have severe disease (p = 0.0011). In multivariate logistic regression model, CAR-T infusion within 6 months (relative risk (RR) 40.92; confidence interval (CI) 4.03-415.89; p = 0.002) were associated with significantly higher risk of severe disease. CONCLUSION: Through this study, we conclude that the outcome for B-cell lymphoma patients following CD19 targeted CAR-T therapy when facing omicron infection was improved, but aggressive precautionary measures were particularly crucial for patients with high risk factors.

Comprehensive analysis of thirteen-gene panel with prognosis value in Multiple Myeloma.

BACKGROUND: Although there are many treatments for Multiple myeloma (MM), patients with MM still unable to escape the recurrence and aggravation of the disease. OBJECTIVE: We constructed a risk model based on genes closely associated with MM prognosis to predict its prognostic value. METHODS: Gene function enrichment and signal pathway enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, univariate and multivariate Cox regression analysis, Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) analysis were used to identify the prognostic gene signature for MM. Finally, the prognostic gene signature was validated using the Gene Expression Omnibus (GEO) database. RESULTS: Thirteen prognostic genes were screened by univariate Cox analysis and LASSO regression analysis. Multivariate Cox analysis revealed risk score to be an independent prognostic factor for patients with MM [Hazard Ratio (HR) = 2.564, 95% Confidence Interval (CI) = 2.223-2.958, P< 0.001]. The risk score had a high level of predictive value according to ROC analysis, with an area under the curve (AUC) of 0.744. CONCLUSIONS: The potential prognostic signature of thirteen genes were assessed and a risk model was constructed that significantly correlated with prognosis in MM patients.

Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent.

BACKGROUND: Recent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting that glucose reduction by energy restriction (calorie restriction or short-term fasting) may has a significant impact on TAMs. The purpose of this study is to verify the effect of fasting-mimicking diet (FMD) on TAMs, and to determine whether FMD synergizes with anti-angiogenic drug apatinib via TAMs. METHODS: The effect of FMD on TAMs and its synergistic effects with apatinib were observed using an orthotopic mouse breast cancer model. An in vitro cell model, utilizing M2 macrophages derived from THP-1 cell line, was intended to assess the effects of low glucose on TAMs under hypoxic and normoxic conditions. Bioinformatics was used to screen for potential mechanisms of action, which were then validated both in vivo and in vitro. RESULTS: FMD significantly inhibit the pro-tumor function of TAMs in vivo and in vitro, with the inhibitory effect being more pronounced under hypoxic conditions. Additionally, the combination of FMD-mediated TAMs inhibition with apatinib results in synergistic anti-tumor activity. This effect is partially mediated by the downregulation of CCL8 expression and secretion by the mTOR-HIF-1α signaling pathway. CONCLUSIONS: These results support further clinical combination studies of FMD and anti-angiogenic therapy as potential anti-tumor strategies.

Spatially Resolved Metabolomics Combined with the 3D Tumor-Immune Cell Coculture Spheroid Highlights Metabolic Alterations during Antitumor Immune Response.

The metabolic cross-talk between tumor and immune cells plays key roles in immune cell function and immune checkpoint blockade therapy. However, the characterization of tumor immunometabolism and its spatiotemporal alterations during immune response in a complex tumor microenvironment is challenging. Here, a 3D tumor-immune cell coculture spheroid model was developed to mimic tumor-immune interactions, combined with mass spectrometry imaging-based spatially resolved metabolomics to visualize tumor immunometabolic alterations during immune response. The inhibition of T cells was simulated by coculturing breast tumor spheroids with Jurkat T cells, and the reactivation of T cells can be monitored through diminishing cancer PD-L1 expressions by berberine. This system enables simultaneously screening and imaging discriminatory metabolites that are altered during T cell-mediated antitumor immune response and characterizing the distributions of berberine and its metabolites in tumor spheroids. We discovered that the transport and catabolism of glutamine were significantly reprogrammed during the antitumor immune response at both metabolite and enzyme levels, corresponding to its indispensable roles in energy metabolism and building new biomass. The combination of spatially resolved metabolomics with the 3D tumor-immune cell coculture spheroid visually reveals metabolic interactions between tumor and immune cells and possibly helps decipher the role of immunometabolic alterations in tumor immunotherapy.