Characterization of Flavor Profiles of Cigar Tobacco Leaves Grown in China via Headspace-Gas Chromatography-Ion Mobility Spectrometry Coupled with Multivariate Analysis and Sensory Evaluation.

Although cigar tobacco leaves (CTLs) have a high economic value, research regarding the flavor characteristics of CTLs is currently limited. A comprehensive study of the flavor characteristics of CTLs from different regions of China was conducted by identifying their volatile-flavor-containing compounds (VFCs) and flavors. The samples were analyzed via gas chromatography-ion mobility spectrometry (GC-IMS) and sensory evaluation. Results revealed considerable differences in the VFC contents of CTLs from different regions of China, suggesting that the VFLs of CTLs could be influenced by geographical origin. Mainly, phenols, pyrazines, and aldehydes were present in the CTLs from Sichuan. High contents of esters and pyrazines were present in the CTLs from Hubei, while esters were the major components of the CTLs from Hainan. Multivariate analysis results showed the effective differentiation of samples from different geographical origins based on the GC-IMS results. Sensory evaluation revealed that the flavors of CTLs from different geographical origins were different. 1,8-Pinene, 3-methyl-3-butene-1-ol, 2,3-dimethyl-5-ethylpyrazine, 4-methyl-3-penten-2-one, and (E)-2-pentenal might serve as geographical marker compounds, indicating the geographical origin of CTLs based on the results of GC-IMS and sensory evaluation. This study may be beneficial for the trade of CTLs and the development of cigar products.

Pan-Cancer Single-Cell and Spatial-Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy.

The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single-cell RNA sequencing (scRNA-seq) and machine learning methods. The scRNA-seq and bulk RNA-seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single-cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan-cancer patients. The proportion of APOE+ macrophages is higher in ICI non-responders of triple-negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor-bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real-world immunotherapy data accurately predicts the ICI response of pan-cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells.

Analysis of differences in aroma and sensory characteristics of the mainstream smoke of six cigars.

Cigars have unique aroma and style characteristics. In order to clarify the differences of aroma components between domestic and imported cigars and the material basis of the stylistic characteristics of different cigars, gas chromatography-mass spectrometry (GC-MS) and sensory evaluation were used to compare and analyze the aroma components in the mainstream smoke of four domestic cigars and two imported cigars. The GC-MS results showed that a total of 97 aroma components were measured in the smoke of the six cigars, and the types of aroma components were similar, but there were differences in their contents. In comparison with those of domestic cigars, imported cigars had suitable nicotine content, and higher contents of phytol, neophytadiene, 3-methylpentanoic acid, and (+)-δ-cadinene. To further explore the differences in the aroma components of the six cigars, GC-MS data combined with chemometrics were used to screen out 14 key aroma components based on P-value (P) < 0.05, Variable Importance Projection (VIP) > 1, and Aroma Activity Values (OAV) > 1. The key aroma components of each cigar were obtained, Snow Dream No. 5: cedrol; Wangguan Guocui: 6-methyl-5-hepten-2-one, pyridine, 2-ethyl-6-methylpyrazine; General Achileus No. 3: p-cresol, 2-methylbutyraldehyde, methyl cyclopentenolone; Montecristo No. 4: cedrol, 2-methylbutyraldehyde, guaiacol, 4-vinylguaiacol, methyl cyclopentenolone; Romeo y Julieta Wide Churchills: cedrol, 2,6-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-heptanone, phenethyl alcohol; Great Wall No. 2: p-cresol, phenethyl alcohol, geranylacetone, methyl cyclopentenolone, dihydroactinidiolide. The odor descriptors of these compounds were consistent with the aroma profiles that were prominent in the senses of each cigar. This experiment initially explored the differences in aroma composition and style characteristics of cigars and provided data to support the quality improvement of domestic cigars.

Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism.

OBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear. METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated. RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment. CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.

Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery.

We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure-activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification.

The magnesium depletion score is associated with increased likelihood of kidney stone disease among female adults.

OBJECT: The association between magnesium depletion score (MDS) and kidney stone disease (KSD) remains unknown. This study was designed to investigate the association of MDS with KSD in adults. METHODS: A total of 19,654 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The MDS was calculated by assessing four aspects, including alcohol assumption, renal function, and use of diuretics and proton pump inhibitor. Multivariable logistic regressions were performed to explore the associations between MDS and the prevalence of KSD. Linear correlations were conducted explore the relationship of testosterone with MDS. RESULTS: In the multivariable logistic regressions with full adjustment for confounding variables, the odds ratio of MDS associating with KSD was 1.28 (95% CI: 1.04-1.58, P = 0.022) in total population, and 1.70 (95% CI: 1.16-2.50, P=0.007) in female participants. Besides, compared to the lowest MDS, the highest MDS was associated with a lower testosterone (ß = -16.39, P=0.009) after full adjustment in non-menopause women. CONCLUSION: This study highlighted a positive correlation of high MDS with KSD in female population, which may be associated low level of serum testosterone.

Aging and mitigation of microplastics during sewage sludge treatments: An overview.

Wastewater treatment plants (WWTPs) receive large quantities of microplastics (MPs) from raw wastewater, but many MPs are trapped in the sludge. Land application of sludge is a significant source of MP pollution. Existing reviews have summarized the analysis methods of MPs in sludge and the effect of MPs on sludge treatments. However, MP aging and mitigation during sludge treatment processes are not fully reviewed. Treatment processes used to remove water, pathogenic microorganisms, and other pollutants in sewage sludge also cause surface changes and degradation in the sludge MPs, affecting the potential risk of MPs. This study integrates MP abundance and distribution in sludge and their aging and mitigation characteristics during sludge treatment processes. The abundance, composition, and distribution of sludge MPs vary significantly with WWTPs. Furthermore, MPs exhibit variable degrees of aging, including rough surfaces, enhanced adsorption potentials for pollutants, and increased leaching behavior. Various sludge treatment processes further intensify these aging characteristics. Some sludge treatments, such as hydrothermal treatment, have efficiently removed MPs from sewage sludge. It is crucial to understand the potential risk of MP aging in sludge and the degradation properties of the MP-derived products from MP degradation in-depth and develop novel MP mitigation strategies in sludge, such as combining hydrothermal treatment and biological processes.

Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway.

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1ß) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.

2D Is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti-Inflammatory Capability.

Polydopamine nanomaterials have emerged as one of the most popular organic materials for the management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfactory because of limited phenolic hydroxyl groups, and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, 2D cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability are reported. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibit three- to fourfold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules are absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms reveal that cationic PDA NSs can concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviate the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid.

Protective Effect of Vitamin K2 (MK-7) on Acute Lung Injury Induced by Lipopolysaccharide in Mice.

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

S100A9+CD14+ monocytes contribute to anti-PD-1 immunotherapy resistance in advanced hepatocellular carcinoma by attenuating T cell-mediated antitumor function.

BACKGROUND: The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application. METHODS: Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance. RESULTS: Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma. CONCLUSIONS: Our study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.

Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial.

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8+ T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 .

Predictive Value of Combined Detection of Serum PSA, PCA3, and Apparent Diffusion Coefficient of Magnetic Resonance Imaging in Bone Metastasis of Prostate Cancer.

Objective: The objective of this study was to examine the utility of combining the detection of serum prostate-specific antigen (PSA), prostate cancer antigen 3 (PCA3), and apparent diffusion coefficient (ADC) of magnetic resonance imaging for predicting bone metastases in prostate cancer. Methods: We looked back at 67 men with prostate cancer who were admitted to our hospital between December 2015 and December 2022. Based on the results of bone metastasis in ECT, men with prostate cancer were split into two groups: those with metastasis (26 cases) and those without (41 cases). The Gleason score, the levels of serum PSA and PCA3, and the difference between ADCmean and the difference between ADCmax and ADCmin (ADCdiff) were compared between the two groups. Results: Patients with bone metastases of prostate cancer exhibited significantly higher levels of PSA, PCA3, ADCmean, and ADCdiffer compared to the control group (P < .05). ADCmean and ADCdiffer were statistically significant (P < .05) greater in the metastatic group compared to the control group. Prostate cancer bone metastasis risk variables were shown to be elevated PSA, PCA3, ADCmean, and big ADCdiffer by logistic regression analysis (P < .05). ROC analysis showed that the AUC curves of PSA, PCA3, ADCmean, ADCmean, and their combination had certain predictive value. Conclusion: Patients with bone metastases of prostate cancer will have drastically different PSA and PCA3 serum values. Risk factors for prostate cancer bone metastases include elevated PSA and PCA3 levels as well as elevated ADCmean and big ADCdiffer. The combination of PSA, PCA3, and MRI ADC values demonstrated a strong predictive value for bone metastasis in prostate cancer patients.

Role of Pmk1, Mpk1, or Hog1 in the mitogen-activated protein kinase pathway of Aspergillus cristatus.

Aspergillus cristatus is a probiotic fungus known for its safety and abundant secondary metabolites, making it a promising candidate for various applications. However, limited progress has been made in researching A. cristatus due to challenges in genetic manipulation. The mitogen-activated protein kinase (MAPK) signaling pathway is involved in numerous physiological processes, but its specific role in A. cristatus remains unclear. In this study, we successfully developed an efficient polyethylene glycol (PEG)-mediated protoplast transformation method for A. cristatus, enabling us to investigate the function of Pmk1, Mpk1, and Hog1 in the MAPK signaling pathway. Our findings revealed that Pmk1, Mpk1, and Hog1 are crucial for sexual reproduction, melanin synthesis, and response to external stress in A. cristatus. Notably, the deletion of Pmk1, Mpk1, or Hog1 resulted in the loss of sexual reproduction capability in A. cristatus. Overall, this research on MAPK will contribute to the continued understanding of the reproductive strategy and melanin synthesis mechanism of A. cristatus.

Mode-division-multiplexing self-homodyne coherent transmission over a weakly coupled few-mode fiber for optical interconnections.

Self-homodyne coherent transmission has recently received extensive investigation as a coherent lite candidate for high-speed short-reach optical networks. In this Letter, we propose a weakly coupled mode-division-multiplexing (MDM) self-homodyne coherent scheme using a multiple-ring-core few-mode fiber, in which one of the modes transmits a self-homodyne local oscillator (LO) and the rest are utilized for carrying signals. Multiple rings of index perturbations in the fiber core are applied to achieve low modal crosstalk, allowing the signals and the remote LO to be transmitted independently. We experimentally demonstrate a 7.2-Tb/s (5.64-Tb/s net rate) self-homodyne coherent transmission with an 800-Gb/s data rate for each of the nine information-bearing modes formatted in 80-GBaud probabilistic constellation-shaped 64-quadrature-amplitude modulation. To the best of our knowledge, this is the first experimental demonstration of an MDM self-homodyne coherent transmission with up to 10 spatial modes. The proposed scheme may pave the way for future high-capacity data center interconnections.

Gradient-descent noise whitening techniques for short-reach IM-DD optical interconnects with severe bandwidth limitation.

Bandwidth limitation in optoelectrical components and the chromatic dispersion-induced power fading phenomenon cause severe inter-symbol interference (ISI) in high-speed intensity modulation and direct detection (IM-DD) optical interconnects. While the equalizer implemented in the receiver's digital signal processing procedure can mitigate ISI, it also inevitably enhances the noise located in the decayed frequency region, known as equalization-enhanced colored noise (EECN). Additionally, the nonlinear impairments of the modulator and photodetector also deteriorate the performance of the IM-DD system, especially for high-order modulation formats. In this work, we propose a gradient-descent noise whitening (GD-NW) algorithm to address EECN and extend it by introducing nonlinear kernels to simultaneously mitigate EECN and nonlinear impairments. The proposed algorithms are compared with conventional counterparts in terms of the achievable baud rate and the receiver optical power sensitivity. As a proof-of-concept experiment, we validate the principles of the proposed algorithms by successfully transmitting 360-GBd on-off-keying (OOK) and 180-GBd 4-level pulse-amplitude-modulation (PAM-4) signals in the back-to-back case under a 62-GHz brick-wall bandwidth limitation. 280-GBd OOK and 150-GBd PAM-4 transmissions are also demonstrated over 1-km standard single-mode fiber with a bit error rate below 7% hard-decision forward error correction aided by the proposed approach.

Evaluation of the Tensile and Puncture Properties of Geotextiles Influenced by Soil Moisture under Freezing Conditions.

Freezing conditions under different humidity will influence the mechanical properties of geotextiles, leading to the gradual fracture of geotextiles. It brings hidden danger to the whole isolation, reinforcement and protection of rock and soil. It is particularly important to study the tensile and puncture properties of geotextiles considering low temperature and moisture content. In this paper, a series of tensile and puncture tests of geotextiles are performed under different low temperatures (0, -3, -6, -9, and -12 °C) and at different moisture content levels (0, 5, 10, 30, 50, and 80%). From the microscopic perspective, the failure mechanism considering the low temperature and moisture content was explained comprehensively. Experimental results indicate that with a decrease in freezing temperature, the tensile strength of geotextiles increases as a parabolic function while the elongation at failure decreases as an exponential function. Additionally, the puncture strength of geotextiles presented a parabolic increase with the decreasing temperature. Under the freezing temperature environment, the higher moisture content of geotextiles can generate a higher puncture strength increment. This research contributes to a more comprehensive understanding of the tensile and puncture properties of geotextile materials considering low temperature and moisture content. It can provide important guidance for the design of slopes, the reinforcement of earthen dams, and roadbed reinforcement with geotextiles in cold regions.

Differential perovskite hemispherical photodetector for intelligent imaging and location tracking.

Advanced photodetectors with intelligent functions are expected to take an important role in future technology. However, completing complex detection tasks within a limited number of pixels is still challenging. Here, we report a differential perovskite hemispherical photodetector serving as a smart locator for intelligent imaging and location tracking. The high external quantum efficiency (~1000%) and low noise (10-13 A Hz-0.5) of perovskite hemispherical photodetector enable stable and large variations in signal response. Analysing the differential light response of only 8 pixels with the computer algorithm can realize the capability of colorful imaging and a computational spectral resolution of 4.7 nm in a low-cost and lensless device geometry. Through machine learning to mimic the differential current signal under different applied biases, one more dimensional detection information can be recorded, for dynamically tracking the running trajectory of an object in a three-dimensional space or two-dimensional plane with a color classification function.

Carbon neutrality endeavors: the impact of carbon emission trading policies on total factor carbon emission efficiency.

Deepening the carbon market allocation reform is a strong support for carbon peaking and carbon neutrality. China has been piloting carbon trading in batches since 2013. However, there is little literature on whether and how carbon emission trading (CET) improves total factor carbon emission efficiency (TFCEE). To fill this gap, this study first calculates urban TFCEE using an extended Epsilon-based model and then designs a quasi-natural experiment based on causal inference. The staggered DID model is adopted to investigate the impact of CET pilot policies on urban TFCEE and its impact mechanism. Our results show that (1) the CET policy has a significant promoting effect on TFCEE in pilot cities, and this conclusion is reconfirmed by adopting robustness tests. (2) The mediating effect models are employed to confirm the mediating role of green technology innovation, industrial structure upgrading, and resource allocation efficiency in CET policy promoting regional TFCEE. (3) The heterogeneity test of CET policy depicts a considerable positive impact on TFCEE in cities with abundant resources. Eastern and developed cities are more likely to experience better carbon efficiency promotion through this policy than other cities. This study provides evidence for the important role of CET in promoting the development of a low-carbon economy and carbon neutrality.

Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

BACKGROUND: Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. METHODS: A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. RESULTS: Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. CONCLUSIONS: At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.