Abrupt reduction in shipping emission as an inadvertent geoengineering termination shock produces substantial radiative warming.

Human activities affect the Earth's climate through modifying the composition of the atmosphere, which then creates radiative forcing that drives climate change. The warming effect of anthropogenic greenhouse gases has been partially balanced by the cooling effect of anthropogenic aerosols. In 2020, fuel regulations abruptly reduced the emission of sulfur dioxide from international shipping by about 80% and created an inadvertent geoengineering termination shock with global impact. Here we estimate the regulation leads to a radiative forcing of +0.2±0.11Wm-2 averaged over the global ocean. The amount of radiative forcing could lead to a doubling (or more) of the warming rate in the 2020 s compared with the rate since 1980 with strong spatiotemporal heterogeneity. The warming effect is consistent with the recent observed strong warming in 2023 and expected to make the 2020 s anomalously warm. The forcing is equivalent in magnitude to 80% of the measured increase in planetary heat uptake since 2020. The radiative forcing also has strong hemispheric contrast, which has important implications for precipitation pattern changes. Our result suggests marine cloud brightening may be a viable geoengineering method in temporarily cooling the climate that has its unique challenges due to inherent spatiotemporal heterogeneity.

A new attempt to remove toluene using nickel-iron bimetallic particle electrode reactor.

A new attempt of removing toluene waste gas using a three-dimensional electrode reaction device with nickel-iron bimetallic particle electrode is presented in this paper. The particle electrode was prepared by a simple liquid phase reduction method. Through bimetal modification, the particle electrode mass transfer rate is increased to 1.29 times, and the degradation efficiency of the reactor is increased by nearly 40%, which makes it possible to remove toluene waste gas by other electrochemical methods in addition to plasma method. The removal efficiency of the particle electrode can be stabilized at more than 80% after 5 cycles (50 h). At the same time, the relationship between independent working parameters and dependent variables is analyzed using the central composite design, and the operating parameters are optimized. Based on this study, the removal mechanism and possible degradation pathway of toluene were investigated. This study provides a supplement to the possibility and theoretical basis of new technology application for electrocatalytic oxidation removal of VOCs.

Effects of T2DM on postoperative outcome of patients with colorectal cancer: a study on the relationship between blood glucose control and survival rate.

To investigate the impact of type 2 diabetes (T2DM) on the prognosis of colorectal cancer (CRC). The data of 312 patients with CRC treated in the First Affiliated Hospital of Huzhou University from 2012 to 2018 were analyzed retrospectively. The patients were divided into a comorbidity group (n = 62) and a non-comorbidity group (n = 250) according to the presence of T2DM. The baseline data of the two groups were balanced by 1:2 propensity score matching (PSM). Kaplan-Meier analysis and Log-rank test were employed to compare the 5-year overall survival (OS) rates of patients. Cox regression model and inverse probability of treatment weighting (IPTW) were utilized to assess the influence of T2DM on 5-year OS of patients. Based on the results of Cox regression, a nomogram model of T2DM on 5-year OS of patients was constructed. A total of 62 patients in the comorbidity group and 124 patients in the non-comorbidity group were matched using PSM. The 5-year OS rate was lower in the comorbidity group than in the non-comorbidity group (82.23% VS 90.32%, P = 0.038). Subgroup analysis showed that the 5-year overall survival rate was higher in the good blood glucose control group than in the poor blood glucose control group (97.14% VS 62.96%, P<0.01). Multivariate Cox regression showed that the 5-year mortality risk in the comorbidity group was 2.641 times higher than that in the non-comorbidity group (P = 0.026). IPTW analysis showed that the 5-year risk of death in the comorbidity group was 2.458 times that of the non-comorbidity group (P = 0.019). The results showed that poor blood glucose control, BMI≥25 kg/m2, low differentiation, III/IV stage, and postoperative infection were independent factors affecting the 5-year overall survival rate of CRC patients (P<0.05). The ROC curve showed that the AUCs of the constructed model in predicting the 5-year OS in the training set and the testing set were 0.784 and 0.776, respectively. T2DM is identified as a risk factor for reduced 5-year survival among CRC patients, necessitating increased attention for this subgroup, particularly those with poor blood glucose control.

Approaches to Improve the Translation of Safety, Pharmacokinetics and Therapeutic Index of ADCs.

Antibody-drug conjugates (ADCs) are an important class of cancer therapies. They are complex molecules, comprising an antibody, a cytotoxic payload, and a linker. ADCs intend to confer high specificity by targeting a unique antigen expressed predominately on the surface of the tumor cells than on the normal cells and by releasing the potent cytotoxic drug inside the tumor causing cytotoxic cell death. Despite high specificity to tumor antigens, many ADCs are associated with off-target and on-target off-tumor toxicities, often leading to safety concerns before achieving the desirable clinical efficacy. Therefore, it is crucial to improve the therapeutic index (TI) of ADCs to enable the full potential of this important therapeutic modality.The review summarizes current approaches to improve the translation of safety, pharmacokinetics, and TI of ADCs. Common safety findings of ADCs resulting from off-target and on-target toxicities and nonclinical approaches to de-risk ADC safety will be discussed; multiple approaches of using preclinical and clinical dose and exposure data to calculate TI to guide clinical dosing will be elaborated; different approaches to improve TI of ADCs, including selecting the right target, right payload-linker and patients, optimizing physicochemical properties, and using fractionation dosing, will also be discussed.

Potential targets and therapeutics for cancer stem cell-based therapy against drug resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common digestive malignancyin the world, which is frequently diagnosed at late stage with a poor prognosis. For most patients with advanced HCC, the therapeutic options arelimiteddue to cancer occurrence of drug resistance. Hepatic cancer stem cells (CSCs) account for a small subset of tumor cells with the ability of self-renewal and differentiationin HCC. It is widely recognized that the presence of CSCs contributes to primary and acquired drug resistance. Therefore, hepatic CSCs-targeted therapy is considered as a promising strategy to overcome drug resistance and improve therapeutic outcome in HCC. In this article, we review drug resistance in HCC and provide a summary of potential targets for CSCs-based therapy. In addition, the development of CSCs-targeted therapeuticsagainst drug resistance in HCC is summarized in both preclinical and clinical trials. The in-depth understanding of CSCs-related drug resistance in HCC will favor optimization of the current therapeutic strategies and gain encouraging therapeutic outcomes.

Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.

PURPOSE: Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap. METHODS: We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169). RESULTS: Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)]. CONCLUSION: In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.

Efficacy and Safety of Hepatic Arterial Infusion Therapy with Cinobufacini in Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Retrospective Cohort Study.

Background: The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI. Methods: The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups. Results: The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40-0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03-2.16; P=0.032) and AFP (>1000; HR, 1.61; 95% CI: 1.08-1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009). Conclusion: Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.

A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study.

BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and albumin levels in plasma, the vitreous humor, the aqueous humor, and retina tissue at various timepoints post-dose. A comprehensive bioanalytical approach was implemented in support of this study. Five immunocapture-LC-MS/MS assays were developed and qualified for quantitating BI-X in different matrices, while ELISA was used for albumin measurement. Immunocapture at the protein or peptide level was evaluated to achieve adequate assay sensitivity. Drug and albumin assays were applied for the analysis of the monkey study samples.

Recent progress of particle electrode materials in three-dimensional electrode reactor: synthesis strategy and electrocatalytic applications.

With the complete promotion of a green, low-carbon, safe, and efficient economic system as well as energy system, the promotion of clean governance technology in the field of environmental governance becomes increasingly vital. Because of its low energy consumption, great efficiency, and lack of secondary pollutants, three-dimensional (3D) electrode technology is acknowledged as an environmentally beneficial and sustainable way to managing clean surroundings. The particle electrode is an essential feature of the 3D electrode reactor. This study provides an in-depth examination of the most current advancements in 3D electrode technology. The significance of 3D electrode technology is emphasized, with an emphasis on its use in a variety of sectors. Furthermore, the particle electrode synthesis approach and mechanism are summarized, providing vital insights into the actual implementation of this technology. Furthermore, by a metrological examination of the research literature in this sector, the paper expounds on the potential and obstacles in the development and popularization of future technology.

Observational evidence of strong forcing from aerosol effect on low cloud coverage.

Aerosols cool Earth's climate indirectly by increasing low cloud brightness and their coverage (Cf), constituting the aerosol indirect forcing (AIF). The forcing partially offsets the greenhouse warming and positively correlates with the climate sensitivity. However, it remains highly uncertain. Here, we show direct observational evidence for strong forcing from Cf adjustment to increased aerosols and weak forcing from cloud liquid water path adjustment. We estimate that the Cf adjustment drives between 52% and 300% of additional forcing to the Twomey effect over the ocean and a total AIF of -1.1 ± 0.8 W m-2. The Cf adjustment follows a power law as a function of background cloud droplet number concentration, Nd. It thus depends on time and location and is stronger when Nd is low. Cf only increases substantially when background clouds start to drizzle, suggesting a role for aerosol-precipitation interactions. Our findings highlight the Cf adjustment as the key process for reducing the uncertainty of AIF and thus future climate projections.

On-Demand Dynamic Terahertz Polarization Manipulation Based on Pneumatically Actuated Metamaterial.

In this paper, a new tuning strategy is proposed by incorporating a pneumatically actuated metamaterial to achieve on-demand polarization manipulation at THz frequencies. Through controlling the actuation pressure, the device function can be flexibly switched among three types of polarization conversion capabilities within the same operation frequency band, from 1.3 THz to 1.5 THz, in which the mutual conversion between linear polarization and circular polarization, such as a quarter-wave plate, and handedness inversion between circular polarizations as a helicity inverter as well as a helicity keeper, have been successfully achieved between the incidence and reflection. Moreover, the intrinsic tuning mechanism for the polarization manipulation is also discussed.

AlN-based piezoelectric MEMS deformable mirror.

An AlN-based piezoelectric micro-electromechanical system (MEMS) continuous membrane deformable mirror (DM) prototype is presented for the first time. Its effective aperture diameter is 5 mm and it is equipped with 25 independently controlled actuators. Owing to the advantages associated with the AlN piezoelectric thin-film technology, attractive characteristics including CMOS compatible fabrication, bidirectional linear and negligible hysteresis actuation, and excellent linear superposition control capability have been successfully demonstrated. Moreover, good optical aberration correction performance is also validated via the surface contour fitting experiment to the Zernike polynomials up to the first 14 orders despite the non-optimized device structure design, representing great application perspective.

Recent advances of artificial intelligence in melanoma clinical practice.

Skin melanoma is a lethal cancer. The incidence of melanoma is increasing rapidly in all regions of the world. Despite significant breakthroughs in melanoma treatment in recent years, precise diagnosis of melanoma is still a challenge in some cases. Even specialized physicians may need time and effort to make accurate judgments. As artificial intelligence (AI) technology advances into medical practice, it may bring new solutions to this problem based on its efficiency, accuracy, and speed. This paper summarizes the recent progress of AI in melanoma-related applications, including melanoma diagnosis and classification, the discovery of new medication, guiding treatment, and prognostic assessment. The paper also compares the effectiveness of various algorithms in melanoma application and suggests future research directions for AI in melanoma clinical practice.

Uniform design and deep learning based liquid lens optimization strategy toward improving dynamic optical performance and lowering driving force.

An efficient optimization strategy for liquid lens combining the uniform design and the deep learning is proposed to achieve improved dynamic optical performance and lowering driving force simultaneously. The membrane of the liquid lens is designed into a plano-convex cross-section, in which the contour function of the convex surface as well as the central membrane thickness is especially optimized. The uniform design method is initially utilized to select a part of uniformly distributed and representative parameter combinations from all possible parameter range, and their performance data is then obtained through simulation using MATLAB to control COMSOL and ZEMAX. After that, a deep learning framework is employed to build a four-layer neural network with its input and output layer representing the parameter combinations and the performance data, respectively. After 5 × 103 epochs, the deep neural network has undergone sufficient training, demonstrating effective performance prediction capability for all parameter combinations. Finally, a "globally" optimized design can be obtained by setting appropriate evaluation criteria which take the spherical aberration, the coma and the driving force into consideration. Compared with the conventional design using uniform membrane thickness of 100 µm and 150 µm as well as the previously reported "locally" optimized design, distinct improvements in the spherical and the coma aberrations across the entire focal length tuning range have been achieved, whilst the required driving force is largely reduced. In addition, the "globally" optimized design exhibits the best modulation transfer function (MTF) curves and provides the best image quality.

Anaerobic purinolytic enzymes enable dietary purine clearance by engineered gut bacteria.

Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.

Comparative review on microbial electrochemical technologies for resource recovery from wastewater towards circular economy and carbon neutrality.

Newly arising concepts such as the circular economy and carbon neutrality motivate resource recovery from wastewater. This paper reviews and discusses state-of-the-art microbial electrochemical technologies (METs), specifically microbial fuel cells (MFCs), microbial electrolysis cells (MECs) and microbial recycling cells (MRCs), which enable energy generation and nutrient recovery from wastewater. Mechanisms, key factors, applications, and limitations are compared and discussed. METs are effective in energy conversion, demonstrating advantages, drawbacks and future potential as specific scenarios. MECs and MRCs exhibited greater potential for simultaneous nutrient recovery, and MRCs offer the best scaling-up potential and efficient mineral recovery. Research on METs should be more concerned with lifespan of materials, secondary pollutants reduction and scaled-up benchmark systems. More up-scaled application cases are expected for cost structures comparison and life cycle assessment of METs. This review could direct the follow-up research, development and successful implementation of METs for resource recovery from wastewater.

Single optical fiber based forward-viewing all-optical ultrasound self-transceiving probe.

All-optical ultrasound probes with fully integrated ultrasound generation and detection functions demonstrate some unique advantages over traditional electroacoustic counterparts. However, due to the lack of an effective solution, the most commonly used method is to assemble two separate functional optical fibers together for ultrasound generation and detection, respectively. In this Letter, an innovative strategy, to the best of our knowledge, is developed to integrate the photoacoustic effect based ultrasound generation and the Fabry-Pérot (FP) interference based ultrasound detection structures together at the end of a single double clad optical fiber (DCF), so as to make a compact forward-viewing ultrasound self-transceiving probe (1-mm diameter). From the experiment results, the as-fabricated probe can generate an ultrasound signal with an amplitude of 2.36 MPa at 2.25 mm in the transmitting mode, and its peak frequency and -6-dB bandwidth are measured to be 10.64 MHz and 22.93 MHz, respectively. When being operated under the receiving mode, the probe has a detection sensitivity of 208.4 mV/MPa for ultrasound signals with the peak frequency of 8.24 MHz, and the noise equivalent pressure (NEP) is 76.8 kPa. In addition, the forward-viewing format ultrasound self-transceiving experiment is also performed and the pulse-echo signal varying with the transmission distance is successfully captured for the first time.