Parasite-enhanced immunotherapy: transforming the "cold" tumors to "hot" battlefields.

Immunotherapy has emerged as a highly effective treatment for various tumors. However, the variable response rates associated with current immunotherapies often restrict their beneficial impact on a subset of patients. Therefore, more effective treatment approaches that can broaden the scope of therapeutic benefits to a larger patient population are urgently needed. Studies have shown that some parasites and their products, for example, Plasmodium, Toxoplasma, Trypanosoma, and Echinococcus, can effectively transform "cold" tumors into "hot" battlefields and reshape the tumor microenvironment, thereby stimulating innate and adaptive antitumor immune responses. These parasitic infections not only achieve the functional reversal of innate immune cells, such as neutrophils, macrophages, myeloid-derived suppressor cells, regulatory T cells, and dendritic cells, in tumors but also successfully activate CD4+/CD8+ T cells and even B cells to produce antibodies, ultimately resulting in an antitumor-specific immune response and antibody-dependent cellular cytotoxicity. Animal studies have confirmed these findings. This review discusses the abovementioned content and the challenges faced in the future clinical application of antitumor treatment strategies based on parasitic infections. With the potential of these parasites and their byproducts to function as anticancer agents, we anticipate that further investigations in this field could yield significant advancements in cancer treatment.

First-principles molecular dynamics study on the behaviors of Cs in a mixed system of liquid metal and LiCl-KCl molten salt.

The structure and dynamic properties of Cs in the mixed system of LiCl-KCl molten salt and a liquid metal (Bi and Pb) electrode are investigated through first-principles molecular dynamics simulation. It is found that the dynamic properties of different ions in molten salt could be significantly affected when the liquid metal electrode is coupled and this influence varies with the type of liquid metal applied. The microstructures of the mixed systems of molten salt and liquid metal electrode: MS-Cs-Bi, MS-CsCl-Bi, MS-Cs-Pb, and MS-CsCl-Pb, are also investigated by the bond angle distribution function, Voronoi tessellation analysis, five-fold symmetry parameter, and bond-orientational order parameter. The comparison study of the microstructures of the mixed systems when different liquid metal electrodes are applied provides information on the liquid metal electrode selection when conducting electrolysis. The present study represents the first demonstration of the study of a mixed system of salt and liquid electrode for practical applications and would be greatly beneficial to the development of pyroprocessing of spent nuclear fuel.

Arabidopsis F-box proteins D5BF1 and D5BF2 negatively regulate Agrobacterium-mediated transformation and tumorigenesis.

The pathogen Agrobacterium tumefaciens is known for causing crown gall tumours in plants. However, it has also been harnessed as a valuable tool for plant genetic transformation. Apart from the T-DNA, Agrobacterium also delivers at least five virulence proteins into the host plant cells, which are required for an efficient infection. One of these virulence proteins is VirD5. F-box proteins, encoded in the host plant genome or the Ti plasmid, and the ubiquitin/26S proteasome system (UPS) also play an important role in facilitating Agrobacterium infection. Our study identified two Arabidopsis F-box proteins, D5BF1 and D5BF2, that bind VirD5 and facilitate its degradation via the UPS. Additionally, we found that Agrobacterium partially suppresses the expression of D5BF1 and D5BF2. Lastly, stable transformation and tumorigenesis efficiency assays revealed that D5BF1 and D5BF2 negatively regulate the Agrobacterium infection process, showing that the plant F-box proteins and UPS play a role in defending against Agrobacterium infection.

Evaluation of outcomes and risk factors for recurrent preeclampsia in a subsequent pregnancy.

PURPOSE: The aim was to evaluate the pregnancy outcomes and identify risk factors for recurrent preeclampsia (PE). METHODS: Retrospective analysis of patients discharged with PE between January 1, 2010, and January 1, 2023, from two tertiary referral hospitals. They were classified into recurrent and non-recurrent groups based on the presence of PE in subsequent pregnancies. RESULTS: Among 519 women who had a subsequent pregnancy after a history of PE, 153 developed recurrent PE while 366 did not. The recurrent cases included 81 preterm PE, of which 41 were early-onset PE (EOPE). Recurrent PE correlated significantly with prior EOPE, HELLP syndrome, placental abruption, and stillbirth, as well as with current chronic hypertension (CH) and type 2 diabetes. The recurrent group showed a 5.8-fold higher risk of preterm birth (PTB) compared to the non-recurrent group (50.7% vs. 8.7%). Notably, 58.1% of the PTBs in the non-recurrent group were spontaneous. Logistic regression identified previous EOPE (aOR: 4.22 [95% CI: 2.50-7.13]) and current CH (aOR: 1.86 [95% CI: 1.09-3.18]) as independent contributors for recurrent PE. Furthermore, recurrent preterm PE shared the same risk factors: previous EOPE (aOR: 5.27 [95% CI: 2.82-9.85]) and current CH (aOR: 2.99 [95% CI: 1.57-5.71]). The morbidity of CH in subsequent pregnancy peaked at 31.9% when women with a history of EOPE delivered within three years. CONCLUSION: Previous EOPE and current CH were sequentially crucial risk factors for the development of PE and preterm PE during the next pregnancy. This may clarify risk stratification in prenatal management for women with a history of PE.

Astrocyte allocation during brain development is controlled by Tcf4-mediated fate restriction.

Astrocytes in the brain exhibit regional heterogeneity contributing to regional circuits involved in higher-order brain functions, yet the mechanisms controlling their distribution remain unclear. Here, we show that the precise allocation of astrocytes to specific brain regions during development is achieved through transcription factor 4 (Tcf4)-mediated fate restriction based on their embryonic origin. Loss of Tcf4 in ventral telencephalic neural progenitor cells alters the fate of oligodendrocyte precursor cells to transient intermediate astrocyte precursor cells, resulting in mislocalized astrocytes in the dorsal neocortex. These ectopic astrocytes engage with neocortical neurons and acquire features reminiscent of dorsal neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during the differentiation of oligodendrocyte precursor cells derived from the ventral telencephalon, thereby restricting the fate to the oligodendrocyte lineage in the dorsal neocortex. Together, our findings highlight a previously unappreciated role for Tcf4 in regulating astrocyte allocation, offering additional insights into the mechanisms underlying neurodevelopmental disorders linked to Tcf4 mutations.

Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS Study.

The superiority and tolerability of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) was previously described in the global phase 3 ALCYONE study. The primary analysis of the phase 3 OCTANS study further demonstrated the superiority and tolerability of D-VMP (n = 144) versus VMP (n = 71) in transplant-ineligible Asian patients with NDMM. The current analysis describes the final efficacy and safety outcomes for D-VMP versus VMP in OCTANS, with a follow-up of > 3 years. D-VMP demonstrated a benefit versus VMP with regard to the rate of very good partial response or better (80.1% vs. 47.3%), median progression-free survival (38.7 vs. 19.2 months), median time to next treatment (46.8 vs. 20.6 months), rate of complete response or better (46.6% vs. 18.9%), median duration of response (41.3 vs. 18.5 months), achievement of minimal residual disease (MRD) negativity (40.4% vs. 10.8%), and sustained MRD negativity for ≥ 12 months (24.7% vs. 1.4%) and ≥ 18 months (15.1% vs. 1.4%). Median progression-free survival was longer among patients who achieved MRD negativity and sustained MRD negativity. The progression-free survival benefit observed with D-VMP was preserved across most clinically relevant subgroups, including patients with high-risk cytogenetics. No new safety concerns were identified with extended follow-up. This final analysis of OCTANS continues to demonstrate a clinical benefit for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM, consistent with the global ALCYONE study, and supports the use of daratumumab combinations in this population. Trial registration: ClinicalTrials.gov Identifier NCT03217812 submitted July 13, 2017.

Apolipoprotein E in patients with undiagnosed pleural effusion: a prospective diagnostic test accuracy study.

INTRODUCTION: Pleural effusion is common in clinical practice, and its differential diagnosis remains challenging for clinicians. This study investigates the diagnostic value of apolipoprotein E (apoE) in patients with undetermined pleural effusion. METHODS: This prospective, double-blind study enrolled 152 patients with undiagnosed pleural effusion. Their pleural fluid apoE levels were measured, and a receiver operating characteristics (ROC) curve was used to evaluate the diagnostic accuracy of apoE. Decision curve analysis (DCA) was used to assess apoE's net benefit. Subgroup analyses were performed to investigate the effect of age on the diagnostic accuracy of apoE. RESULTS: Among the included participants, 23 had heart failure (HF). HF patients had the lowest apoE level among pleural effusion patients. The area under the curve (AUC) of apoE for HF was 0.79 (95% CI: 0.69-0.89). At the threshold of 40 mg/L, the sensitivity and specificity of apoE were 0.96 (95% CI: 0.87-1.00) and 0.33 (95% CI: 0.25-0.42), respectively. The decision curve for apoE was above reference lines. The AUC of apoE decreased in older patients. CONCLUSION: Pleural fluid apoE has moderate diagnostic value for HF and has net benefits in patients with undiagnosed pleural effusion. The diagnostic accuracy of apoE decreases with age.

Vapor Growth of All-Inorganic 2D Ruddlesden-Popper Lead- and Tin-Based Perovskites.

The 2D Ruddlesden-Popper (RP) perovskites Cs2PbI2Cl2 (Pb-based, n = 1) and Cs2SnI2Cl2 (Sn-based, n = 1) stand out as unique and rare instances of entirely inorganic constituents within the more expansive category of organic/inorganic 2D perovskites. These materials have recently garnered significant attention for their strong UV-light responsiveness, exceptional thermal stability, and theoretically predicted ultrahigh carrier mobility. In this study, we synthesized Pb and Sn-based n = 1 2D RP perovskite films covering millimeter-scale areas for the first time, utilizing a one-step chemical vapor deposition (CVD) method under atmospheric conditions. These films feature perovskite layers oriented horizontally relative to the substrate. Multilayered Cs3Pb2I3Cl4 (Pb-based, n = 2) and Cs3Sn2I3Cl4 (Sn-based, n = 2) films were also obtained for the first time, and their crystallographic structures were refined by combining X-ray diffraction (XRD) and density functional theory (DFT) calculations. DFT calculations and experimental optical spectroscopy support band-gap energy shifts related to the perovskite layer thickness. We demonstrate bias-free photodetectors using the Sn-based, n = 1 perovskite with reproducible photocurrent and a fast 84 ms response time. The present work not only demonstrates the growth of high-quality all-inorganic multilayered 2D perovskites via the CVD method but also suggests their potential as promising candidates for future optoelectronic applications.

CCL5/CCR5/CYP1A1 pathway prompts liver cancer cells to survive in the combination of targeted and immunological therapies.

Combination therapy of anti-programmed cell death protein-1 (PD-1) antibodies and tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis for hepatocellular carcinoma (HCC), but many patients still have unsatisfactory outcomes. CD8 T cells are known to exert a pivotal function in the immune response against tumors. Nevertheless, most CD8 T cells in HCC tissues are in a state of exhaustion, losing the cytotoxic activity against malignant cells. Cytokines, mainly secreted by immune cells, play an important role in the occurrence and development of tumors. Here, we demonstrated the changes in exhausted CD8T cells during combination therapy by single-cell RNA sequencing (scRNA-seq) analysis on tumor samples before and after treatment. Combination therapy exerted a substantial impact on the exhausted CD8T cells, particularly in terms of cytokine expression. CCL5 was the most abundantly expressed cytokine in CD8T cells and exhausted CD8T cells, and its expression increased further after treatment. Subsequently, we discovered the CCL5/CCR5/CYP1A1 pathway through RNA sequencing (RNA-seq) on CCL5-stimulated Huh7 cells and verified through a series of experiments that this pathway can mediate the resistance of liver cancer cells to lenvatinib. Tissue experiments showed that after combination therapy, the CCL5/CCR5/CYP1A1 pathway was activated, which can benefit the residual tumor cells to survive treatment. Tumor-bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC.

Identification and validation of inflammatory subtypes in intrahepatic cholangiocellular carcinoma.

BACKGROUND: Inflammation plays a critical role in tumor development. Inflammatory cell infiltration and inflammatory mediator synthesis cause changes in the tumor microenvironment (TME) in several cancers, especially in intrahepatic cholangiocellular carcinoma (ICC). However, methods to ascertain the inflammatory state of patients using reliable biomarkers are still being explored. METHOD: We retrieved the RNA sequencing and somatic mutation analyses results and the clinical characteristics of 244 patients with ICC from published studies. We performed consensus clustering to identify the molecular subtypes associated with inflammation. We compared the prognostic patterns, clinical characteristics, somatic mutation profiles, and immune cell infiltration patterns across inflammatory subtypes. We performed quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to confirm gene expression. We performed logistic regression analyses to construct a nomogram predicting the inflammatory status of patients with ICC. RESULTS: Our results confirmed that ICC can be categorized into an inflammation-high subtype (IHS) and an inflammation-low subtype (ILS). Patients from each group had distinct prognosis, clinical characteristics, and TME composition. Patients with ICC in the IHS group showed poorer prognosis owing to the immunosuppressive microenvironment and high frequency of KRAS and TP53 mutations. Cancer-associated fibroblast (CAF)-derived COLEC11 reduced myeloid inflammatory cell infiltration and attenuated inflammatory responses. The results of qRT-PCR and IHC experiments confirmed that COLEC11 expression levels were significantly reduced in tumor tissues compared to those in paracancerous tissues. Patients with ICC in the IHS group were more likely to respond to treatment with immune checkpoint inhibitors (ICIs) owing to their higher tumor mutational burden (TMB) scores, tumor neoantigen burden (TNB) scores, neoantigen counts, and immune checkpoint expression levels. Finally, we developed a nomogram to effectively predict the inflammatory status of patients with ICC based on their clinical characteristics and inflammatory gene expression levels. We evaluated the calibration, discrimination potential, and clinical utility of the nomogram. CONCLUSION: The inflammatory response in IHS is primarily induced by myeloid cells. COLEC11 can reduce the infiltration level of this group of cells, and myeloid inflammatory cells may be a novel target for ICC treatment. We developed a novel nomogram that could effectively predict the inflammatory state of patients with ICC, which will be useful for guiding individualized treatment plans.

Self-Growing Hydrogel Bioadhesives for Chronic Wound Management.

Hydrogel bioadhesives have emerged as a promising alternative to wound dressings for chronic wound management. However, many existing bioadhesives do not meet the functional requirements for efficient wound management through dynamically mechanical modulation, due to the reduced wound contractibility, frequent wound recurrence, incapability to actively adapt to external microenvironment variation, especially for those gradually-expanded chronic wounds. Here, a self-growing hydrogel bioadhesive (sGHB) patch that exhibits instant adhesion to biological tissues but also a gradual increase in mechanical strength and interfacial adhesive strength within a 120-h application is presented. The gradually increased mechanics of the sGHB patch could effectively mitigate the stress concentration at the wound edge, and also resist the wound expansion at various stages, thus mechanically contracting the chronic wounds in a programmable manner. The self-growing hydrogel patch demonstrated enhanced wound healing efficacy in a mouse diabetic wound model, by regulating the inflammatory response, promoting the faster re-epithelialization and angiogenesis through mechanical modulation. Such kind of self-growing hydrogel bioadhesives have potential clinical utility for a variety of wound management where dynamic mechanical modulation is indispensable.

Pleural pro-gastrin releasing peptide is a potential diagnostic marker for malignant pleural effusion induced by small-cell lung cancer.

Background: Serum pro-gastrin releasing peptide (proGRP) is a well-recognized diagnostic marker for small cell lung cancer (SCLC). Pleural effusion is common in patients with advanced SCLC. The diagnostic accuracy of pleural proGRP for malignant pleural effusion (MPE) has not yet been established. This study aimed to evaluate the diagnostic accuracy of pleural proGRP for MPE. Methods: We prospectively recruited patients with undiagnosed pleural effusions from two centers (Hohhot and Changshu). An electrochemiluminescence immunoassay was used to detect pleural fluid proGRP. The diagnostic accuracy of proGRP for MPE was evaluated using a receiver operating characteristic (ROC) curve. Results: In both the Hohhot (n=153) and Changshu (n=58) cohorts, pleural proGRP in MPE patients did not significantly differ from that in patients with benign pleural effusions (BPEs) (Hohhot, P=0.91; Changshu, P=0.12). In the Hohhot and Changshu cohorts, the areas under the curves (AUCs) of proGRP were 0.51 [95% confidence interval (CI): 0.41-0.60] and 0.62 (95% CI: 0.47-0.77), respectively. However, patients with SCLC-induced MPE had significantly higher proGRP levels than those with BPE and other types of MPE (P=0.001 for both). In the pooled cohort, the AUC of proGRP for SCLC-induced MPE was 0.90 (95% CI: 0.78-1.00, P=0.001). At a threshold of 40 pg/mL, proGRP had a sensitivity of 1.00 (95% CI: 0.61-1.00) and specificity of 0.59 (95% CI: 0.52-0.66). The positive likelihood ratio was 2.61 (95% CI: 1.99-3.41), and the negative likelihood ratio was 0. Conclusions: Pleural proGRP has no diagnostic value for MPE, but has high diagnostic accuracy for SCLC-induced MPE. In patients with proGRP levels <40 pg/mL, MPE secondary to SCLC can be excluded.

Numerical study on the stimulation effect of boundary sealing and hot water injection in marine challenging gas hydrate extraction.

This study proposed a novel development mode combining boundary sealing and hot water injection to address the challenges of gas leakage, limited reservoir sensible heat, boundary water intrusion, and low productivity faced by challenging hydrate extraction, and the stimulation effect was numerically investigated with Shenhu hydrates as the geological background. The results showed that lower boundary permeability facilitated pressure propagation and achieved volumetric dissociation of hydrates, whereas insufficient formation energy resulted in substantial gas retention. Hot water injection was effective for stimulation, but open boundaries could not maintain the high injection pressure, leading to massive hot water losses and gas escapes. However, their combination achieved a synergistic stimulation like "1 + 1 > 2" because a piston water drive similar to secondary recovery in oil and gas development was formed. Relative to three-spot well patterns, the five-spot shortened the extraction cycle by 680 days and enhanced the gas-to-water ratio by 17%. Increasing injection pressure enhanced water yield more significantly while the improvement of gas yield was more significant by increasing hot water temperature. Overall, high-pressure and high-temperature injection was suggested for gas enhancement and water control. These findings provide important guidance for advancing the commercial development of challenging hydrates.

Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma.

OBJECTIVE: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first-in-human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). METHODS: This is a multicenter phase I clinical trial consisting of the 3+3 dose-escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28-day cycle. RESULTS: Twenty-five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose-limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any-grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time-to-plasma peak concentration of 0.8-1.5 h. The mean half-life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response-evaluable patients, 63.7% achieved stable disease or better. CONCLUSIONS: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose-expansion phase.

Adverse events following immunization of co- and separate administration of DTaP-IPV/Hib vaccines: A real-world comparative study.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

Safety and efficacy of CT-guided percutaneous radiofrequency ablation for non-small cell lung cancer: a single-center, single-arm analysis.

Non-small cell lung cancer (NSCLC) is a prevalent malignant tumor, and the commonly treatment modalities include surgery, radiotherapy, chemotherapy, etc. Currently, CT-guided percutaneous radiofrequency ablation (RFA) for the treatment of cancers has been widely performed. This study aimed to evaluate the safety and efficacy of this therapy in NSCLC patients. Thirty-five NSCLC patients were enrolled in this study and all received CT-guided percutaneous RFA therapy. The outcome measures included the changes in forced respiratory volume in the first second (FEV1), total lung volume (TLC), lesion size and computed tomography (CT) values of the region of interest (ROI) before and after treatment. The main efficacy measures comprised complete tumor ablation and local recurrence after initial treatment, as well as the objective response rate (ORR) and disease control rate (DCR) after 6 months of treatment. After receiving CT-guided percutaneous RFA therapy, the target lesion was effectively controlled and CT values gradually decreased. Besides, no significant changes were observed in the patient's lung function, postoperative complications were experienced by a total of 10 patients, primarily including pneumothorax, infection, lung hollowing. Fortunately, all these complications were successfully managed with appropriate treatment. Following the initial RFA treatment, 31 patients (88.57%) achieved complete ablation, while 6 patients experienced local recurrence. After 6 months of treatment, the ORR and DCR were found to be 68.57% and 82.86% respectively. CT-guided percutaneous RFA has demonstrated favorable safety and efficacy in the treatment of patients with NSCLC at different stages, which represented a promising therapeutic modality.

New Perspective to Evaluate the Carbon Offsetting by Urban Blue-Green Infrastructure: Direct Carbon Sequestration and Indirect Carbon Reduction.

Urban blue-green infrastructure (BGI) offers a multitude of ecological advantages to residents, thereby playing a pivotal role in fortifying urban resilience and fostering the development of climate-resilient cities. Nonetheless, current research falls short of a comprehensive analysis of BGI's overall potential for carbon reduction and its indirect carbon reduction impact. To fill this research gap, we utilized the integrated valuation of ecosystem services and trade-offs model and remote sensing estimation algorithm to quantify the direct carbon sequestration and resultant indirect carbon reduction facilitated by the BGI within the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) (China). To identify the regions that made noteworthy contributions to carbon offsets and outliers, spatial autocorrelation analysis was also employed. The findings of this study reveal that in 2019, the BGI within the study area contributed an overall carbon offset of 1.5 × 108 t·C/yr, of which 3.5 × 107 and 11.0 × 107 t·C/yr were the result of direct carbon sequestration and indirect carbon reduction, respectively. The GBA's total CO2 emissions were 1.1 × 108 t in 2019. While the direct carbon sequestration offset 32.0% of carbon emissions, the indirect carbon reduction mitigated 49.9% of potential carbon emissions. These results highlight the critical importance of evaluating BGI's indirect contribution to carbon reduction. The findings of this study provide a valuable reference for shaping management policies that prioritize the protection and restoration of specific areas, thereby facilitating the harmonized development of carbon offset capabilities within urban agglomerations.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.