Psychosocial Clusters and Their Associations with Depression, Anxiety and Stress Among Older Adults in Shanghai Communities: Results from a Longitudinal Study.

Purpose: Psychosocial factors have been found to profoundly impact mental health of older adults, but the main focus in the current literature has been on one particular aspect of these factors. This study aimed to identify latent classes of older adults based on four psychosocial factors (loneliness, social isolation, perceived social support, and social capital) and the transition of classes over 6 months. We also sought to assess the predictive role of changes in these classes in relation to depression, anxiety, and stress at 18-month follow-up. Methods: We analyzed longitudinal data from 581 community-dwelling older adults in Shanghai, China. The data were collected at baseline (T0), 6-month follow-up (T1) and 18-month follow-up (T2) between March 2021 and April 2023. Using latent class analysis, we identified three underlying classes (Social Connectors, Subjective Social Isolates, and Social Isolates) of the sample. We also established five transition categories from T0 to T1 (Social Connectors T0-T1, Subjective Social Isolates T0-T1, Social Isolates T0-T1, Good Transition, and Bad Transition) using latent transition analysis. Logistic regression was employed to examine the temporal relationships between these transition categories and subsequent symptoms of depression, anxiety and stress, adjusting for age, sex, education, marital status, family income level, sleep quality, health status and outcome variables at T0. Results: Multivariable associations revealed that compared to older adults with persistent good social environment (Social Connectors T0-T1), those with persistent high levels of loneliness and social isolation and low levels of perceived social support and social capital (Social Isolates T0-T1), and those who shifted towards a poorer social environment (Bad Transition) were more likely to experience depression, anxiety and stress at T2. Sustained subjective social isolation (Subjective Social Isolates T0-T1) was associated with more severe depressive symptoms at T2. Conclusion: Our study indicated that adverse psychosocial environment worsened mental health in older adults. These findings highlight the importance of early identification of older individuals at long-term psychosocial risk and development of tailored interventions to improve their social environment and mental health.

Hierarchical multi-level dynamic hyperparameter deformable image registration with convolutional neural network.

Objective. To enable the registration network to be trained only once, achieving fast regularization hyperparameter selection during the inference phase, and to improve registration accuracy and deformation field regularity.Approach. Hyperparameter tuning is an essential process for deep learning deformable image registration (DLDIR). Most DLDIR methods usually perform a large number of independent experiments to select the appropriate regularization hyperparameters, which are time-consuming and resource-consuming. To address this issue, we propose a novel dynamic hyperparameter block, which comprises a distributed mapping network, dynamic convolution, attention feature extraction layer, and instance normalization layer. The dynamic hyperparameter block encodes the input feature vectors and regularization hyperparameters into learnable feature variables and dynamic convolution parameters which changes the feature statistics of the high-dimensional features layer feature variables, respectively. In addition, the proposed method replaced the single-level structure residual blocks in LapIRN with a hierarchical multi-level architecture for the dynamic hyperparameter block in order to improve registration performance.Main results. On the OASIS dataset, the proposed method reduced the percentage of the negative Jacobian determinant by 28.01%, 9.78% and improved Dice similarity coefficient by 1.17%, 1.17%, compared with LapIRN and CIR, respectively. On the DIR-Lab dataset, the proposed method reduced the percentage of the negative Jacobian determinant by 10.00%, 5.70% and reduced target registration error by 10.84%, 10.05%, compared with LapIRN and CIR, respectively.Significance. The proposed method can fast achieve the corresponding registration deformation field for arbitrary hyperparameter value during the inference phase. Extensive experiments demonstrate that the proposed method reduces training time compared to DLDIR with fixed regularization hyperparameters while outperforming the state-of-the-art registration methods concerning registration accuracy and deformation smoothness on brain dataset OASIS and lung dataset DIR-Lab.

Profiling of viral load, antibody and inflammatory response of people with monkeypox during hospitalization: a prospective longitudinal cohort study in China.

BACKGROUND: The dynamics of viral shedding and the specific humoral response against monkeypox virus (MPXV) have not been well characterized in patients across their disease course during hospitalisation. The aim of this study was to determine the viral load and the levels of antibodies against MPXV using longitudinal paired-collected samples from hospitalized patients. METHODS: Patients who were hospitalised with mpox were recruited at Beijing Ditan Hospital Capital Medical University in China between June 2 and September 23, 2023. Paired samples, including samples from skin lesions, the oropharynx, saliva, faeces, urine, plasma, and serum, were serially collected at days 1, 3, 7, and 14 after admission until discharge. Not all of the patients had samples obtained at all of the timepoints. All the samples were analysed via quantitative PCR. Virus isolation was performed by using clinical samples and Vero cells. The presence of IgM, IgA, IgG, and neutralising antibodies (NAbs) against MPXV was evaluated. The first collected plasma sample was taken when the patient was hospitalised, and the levels of cytokines and chemokines were measured in the sample. The demographic data, smallpox vaccination status, history of known exposure to MPVX, HIV status and other clinical data were collected using a standard case report form. FINDINGS: A total of 510 specimens were serially collected from 39 recruited people with mpox. Among all the samples, the skin lesions had the highest viral DNA detection rates and viral loads, and the saliva samples had the second highest rates and viral loads. One day before discharge, 85% of the dry scrabs (median Ct 28.2, range 19.0-38.3) and 70% of the saliva samples (median Ct 32.4, range 24.5-38.1) were positive for viral DNA, Of which, 23.1% of dry scrabs were positive in viral culture. The rate of viral DNA detection in the oropharyngeal, saliva, and faecal samples decreased with time, while the rates in the plasma, serum, and urine samples increased quickly before 10 days post symptom onset (PSO). The median days of appearance of MPXV-IgM, MPXV-IgA, MPXV-IgG, and NAb were at 8 (interquartile range [IQR] 7-9), 9 (7-10), 12 (9-15), and 12 (9-15) PSO, respectively. The IgM, IgA, IgG, and NAb titres increased with time. Between days 11 and 21 PSO, the NAb titres were lower in people living with HIV (PWH) than in people living without HIV (PWOH). Increased NAb titres were associated with decreased viral loads in the saliva (r = 0.28, p = 0.025), faeces (r = 0.35, p = 0.021), plasma (r = 0.30, p = 0.0044), and serum samples (r = 0.37, p = 0.001). Compared with PWOH, PWH had higher plasma levels of MIP-1α, MIP-1ß, G-CSF, IL-4, and FGF-basic. INTERPRETATION: The high positive viral culture rate of clinical samples of patients when they are discharged from the hospital indicates that effective public health management strategies are needed for people with mpox. The low NAb titres and high levels of cytokines in PWH shows that earlier treatment is needed to control inflammation in high-risk populations. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences, Fundamental Research Funds for the Central Universities for Peking Union Medical College, National Key R&D Program of China.

Health Care Resource Use for Modern First-Line Treatments in Metastatic Renal Cell Carcinoma.

Importance: Immuno-oncology agents have changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). Such therapies improve survival but can impose considerable health care resource use (HCRU) and associated costs, necessitating their examination. Objective: To compare HCRU, costs, and clinical outcomes among patients receiving first-line pembrolizumab plus axitinib (P+A) or ipilimumab plus nivolumab (I+N). Design, Setting, and Participants: This retrospective cohort study used data from an administrative claims database on patients with mRCC receiving first-line P+A or I+N that was initiated between January 2018 and May 2020. Data were analyzed from February 2021 to July 2022. Exposure: First-line P+A or I+N. Main Outcome and Measures: HCRU and costs during the first 90 days, full first-line treatment, and full follow-up periods were assessed. Using Kaplan-Meier analysis, time on treatment, overall survival, time to first emergency department (ED) visit, and time to first inpatient stay were compared. Results: Among 507 patients, there were 126 patients receiving P+A (91 male [72.2%]; mean [SD] age, 67.93 [9.66] y) and 381 patients receiving I+N (271 male [71.1%]; mean [SD] age, 66.52 [9.94] years). The median time on treatment was longer for the P+A compared with I+N group (12.4 months [95% CI, 8.40 months to not estimable] vs 4.1 months [95% CI, 3.07 to 5.30 months]; P < .001). The median time to first ED visit was longer for the P+A than I+N group (7.2 months [95% CI 3.9 to 11.1 months ] vs 3.3 months [95% CI, 2.6 to 3.9 months]; P = .005), as was time to first inpatient stay (9.0 months [95% CI 6.5 months to not estimable] vs 5.6 months [95% CI, 3.9 to 7.9 months]; P = .02). During the first 90 days, a lower proportion of the P+A than N+I group had ED visits (43 patients [34.1%] vs 182 patients [47.8%] and inpatient stays (24 patients [19.1%) vs144 patients [37.8%]; P < .001). During full follow-up, mean total adjusted costs were similar for P+A and I+N groups, but adjusted 12-month estimated total costs were higher for P+A than I+N groups ($325 574 vs $ 263 803; P = .03). Conclusions and Relevance: In this study, treatment with P+A was associated with longer time on treatment, time to first ED visit, and inpatient stay, while 12-month estimated costs were higher for the P+A group. This is among the first clinical studies to evaluate economic burden associated with modern treatments for mRCC.

Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy: A case report.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

Coffee, PI3K signaling pathway, and prostate cancer: a prospective study in the Health Professionals Follow-up Study.

BACKGROUND: Higher coffee intake has been associated with reduced risk of prostate cancer, particularly aggressive forms. The activation of the PI3K signaling pathway plays an important role in prostate carcinogenesis. OBJECTIVE: To evaluate associations between pre-diagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-up Study, a prospective cohort study conducted in the US. DESIGN: A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every four years thereafter until prostate cancer diagnosis. PARTICIPANTS/SETTING: Study participants comprised 1,242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens. MAIN OUTCOME MEASURES: The outcomes include the PI3K activation score; expression of insulin receptor and IGF1 receptor; angiogenesis markers; and presence of the tumor suppressor PTEN, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia. STATISTICAL ANALYSES PERFORMED: Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence. RESULTS: Among coffee drinkers (86.6% of the population), median (25th-75th) coffee intake was 2 (1-3) cups/day. The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 cups/day of coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for PTEN loss, IGF1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58. CONCLUSIONS: Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association.

Brain-machine interactive neuromodulation research tool with edge AI computing.

Closed-loop neuromodulation with intelligence methods has shown great potentials in providing novel neuro-technology for treating neurological and psychiatric diseases. Development of brain-machine interactive neuromodulation strategies could lead to breakthroughs in precision and personalized electronic medicine. The neuromodulation research tool integrating artificial intelligent computing and performing neural sensing and stimulation in real-time could accelerate the development of closed-loop neuromodulation strategies and translational research into clinical application. In this study, we developed a brain-machine interactive neuromodulation research tool (BMINT), which has capabilities of neurophysiological signals sensing, computing with mainstream machine learning algorithms and delivering electrical stimulation pulse by pulse in real-time. The BMINT research tool achieved system time delay under 3 ms, and computing capabilities in feasible computation cost, efficient deployment of machine learning algorithms and acceleration process. Intelligent computing framework embedded in the BMINT enable real-time closed-loop neuromodulation developed with mainstream AI ecosystem resources. The BMINT could provide timely contribution to accelerate the translational research of intelligent neuromodulation by integrating neural sensing, edge AI computing and stimulation with AI ecosystems.

Effects of Different Exercise Intensities on the Rat Model of Heart Failure.

Heart failure (HF) is a clinical syndrome caused by the progression of various cardiac diseases to severe stages, and exercise training plays a positive role in the development of HF. This study aimed to investigate the impact of different intensities of exercise training on HF rats.In this study, we established two HF rat models by intraperitoneal injection of isoproterenol at 2.5 mg/kg/day and abdominal aortic coarctation. After exercise training for 4 weeks, the heart weight/body weight ratio and echocardiography results were measured. Moreover, the regulatory effect of different exercise intensities on myocardial function in HF model rats was verified using tissue staining, western blotting, and reagent kits.Exercise training had a bidirectional adjust effect on HF. A running training program of 20 minutes/time had the most significant effect on improving myocardial function in HF rats, whereas exercise intensity of 40 minutes/time or 50 minutes/time did not significantly improve myocardial function in HF rats. Moreover, exercise intensities of 20 minutes/time and 30 minutes/time could reduce the expression levels of the HF markers NT-proBNP and BNP in rats, but the effect was more significant at a duration of 20 minutes/time. We also found that compared with other exercise intensities, 20 minutes/time exercise intensity could significantly improve myocardial fibrosis, promote cardiomyocyte autophagy, and reduce apoptosis in combating HF.Furthermore, an exercise intensity of 20 minutes/time can significantly ameliorate the progression of HF. However, the degree of significance of increasing exercise intensity in improving HF progression is weakened or has no significant effect.

Mechanisms of litter input changes on soil organic carbon dynamics: a microbial carbon use efficiency-based perspective.

Plant litter is an important source of soil organic carbon (SOC) in terrestrial ecosystems, and the pattern of litter inputs is also influenced by global change and human activities. However, the current understanding of the impact of changes in litter inputs on SOC dynamics remains contentious, and the mechanisms by which changes in litter inputs affect SOC have rarely been investigated from the perspective of microbial carbon use efficiency (CUE). We conducted a 1-year experiment with litter treatments (no aboveground litter (NL), natural aboveground litter (CK), and double aboveground litter (DL)) in Robinia pseudoacacia plantation forest on the Loess Plateau. The objective was to assess how changes in litter input affect SOC accumulation in forest soils from the perspective of microbial CUE. Results showed that NL increased soil microbial C limitation by 77.11 % (0-10 cm) compared to CK, while it had a negligible effect on nitrogen and phosphorus limitation. In contrast, DL had no significant effect on soil microbial nutrient limitation. Furthermore, NL was found to significantly increase microbial CUE and decrease microbial metabolic quotient (QCO2), while the opposite was observed with DL. It is noteworthy that NL significantly contributed to an increase in SOC of 30.72 %, while DL had no significant effect on SOC. Correlation analysis showed that CUE was directly proportional to SOC and inversely proportional to QCO2. The partial least squares pathway model indicated that NL indirectly regulated the accumulation of SOC, mainly through two pathways: promoting microbial CUE increase and reducing QCO2. Overall, this study elucidates the mechanism and novel insights regarding SOC accumulation under changes in litter input from the perspective of microbial CUE. These findings are critical for further comprehension of soil carbon dynamics and the terrestrial C-cycle.

Efficacy of technology-based cognitive and exercise interventions for mild cognitive impairment: A systematic review, network meta-analysis, and meta-regression of randomized controlled trials.

BACKGROUND: Technology has been increasingly integrated into controlling the decline of cognitive function. It is unclear whether technology-based cognitive and exercise interventions (T-CEIs) could generate synergistic benefits and what components would optimize this effect. This study aimed to compare the effectiveness of various T-CEIs on cognitive function in individuals with mild cognitive impairment (MCI). METHODS: In this study, we searched MEDLINE, Web of Science, Scopus, Embase, and APA PsycInfo from inception to November 4, 2023. We included randomized controlled trials that evaluated the effects of T-CEIs on cognitive function for individuals with MCI. The primary outcome was global cognition. The outcomes were summarized in narrative synthesis and combined using meta-analysis. Pairwise meta-analysis and network meta-analysis were sequentially performed to investigate the effects of each category of interventions and their comparative intervention effectiveness, respectively. Meta-regression was performed to examine the influence of study design and participants' characteristics on the intervention effectiveness. This systematic review protocol was registered in PROSPERO (CRD 42023486359). RESULTS: Twenty-eight studies with 1633 participants were included. The results of pairwise meta-analyses indicated that T-CEIs were superior to active/passive controls in improving global cognition, cognitive shifting, processing speed, working memory, delayed recall, and category fluency (p < 0.05). The results of network meta-analyses indicated that the optimal components in improving global cognition (SUCRA 77.0%, SMD 0.85, 95% CI -0.17 to 1.87) and cognitive shifting (SUCRA 92.4%, SMD 1.57, 95% CI 0.88-2.25) were cognitive stimulation (CS) combined with mind-body exercise (MBE), while cognitive training combined with MBE was the most beneficial in developing processing speed (SUCRA 88.5%, SMD 0.68, 95% CI 0.14-1.22). Meta-regression further suggested that the effects of the tested interventions were independent of the various factors related to study design and participants' characteristics. CONCLUSIONS: T-CEIs are effective in improving global cognition and core subdomains of cognition in individuals with MCI. This review highlights the superior effects of technology-based CS combined with MBE in improving global cognition.

Analysis of the therapeutic effect of synchronous integrated intensity modulated radiotherapy combined with chemotherapy in stage IIIc of cervical cancer.

Objective: To explore the Therapeutic effect of synchronous Integrated intensity modulated radiotherapy combined with chemotherapy in stage IIIc of Cervical Cancer. Methods: A total of 58 patients with stage IIIC cervical cancer (KPS ≥ 80) were analyzed in this study. They were admitted to our hospital between August 2017 and August 2022. Synchronous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and sequential boost intensity-modulated radiotherapy (LCB-IMRT) were used to treat pelvic and/or para-aortic metastatic lymph nodes, with 30 cases in the SIB group and 28 cases in the LCB group. Comparison of short-term and long-term efficacy. Comparison of recurrence and metastasis rates, radiation dose to organs at risk and incidence of adverse drug reactions. Result: 30 patients were treated with simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT), and 28 patients were treated with sequential boost intensity-modulated radiotherapy (LCB-IMRT). At the completion of radiotherapy and 3 months after radiotherapy, there was no significant difference in clinical efficacy observed between the two treatment groups. The median overall survival (OS), progression-free survival (PFS), and disease-free survival (DMR) in the SIB-IMRT group were significantly higher compared to the LCB-IMRT group. The SIB-IMRT group demonstrated significantly lower rates compared to the LCB-IMRT group. Furthermore, within 3 years and 5 years, the rates of lymph node recurrence, cervical and vaginal local recurrence, and distant metastasis within the radiotherapy field were significantly lower in the SIB-IMRT group compared to the LCB-IMRT group. There were no significant differences observed between the two groups in terms of the maximum dose to the small intestine (Dmax), dose received by 2cc of the small intestine (D2cc), maximum dose to the rectum (Dmax), and dose received by 1cc of the bladder (D1cc). The incidence of bone marrow toxicity in the SIB-IMRT group was significantly lower compared to the LCB-IMRT group. Moreover, the occurrence of grade III and IV bone marrow toxicity was also significantly lower in the SIB-IMRT group compared to the LCB-IMRT group. Conclusion: The study has concluded that there is no significant differences in in terms of bladder associated adverse events and gastrointestinal toxicity in both Simultaneous Integrated Boost Intensity-Modulated Radiotherapy and Layered Conical Beam Intensity-Modulated Radiation Therapy.

Semantic Aware Stitching for Panorama.

The most critical aspect of panorama generation is maintaining local semantic consistency. Objects may be projected from different depths in the captured image. When warping the image to a unified canvas, pixels at the semantic boundaries of the different views are significantly misaligned. We propose two lightweight strategies to address this challenge efficiently. First, the original image is segmented as superpixels rather than regular grids to preserve the structure of each cell. We propose effective cost functions to generate the warp matrix for each superpixel. The warp matrix varies progressively for smooth projection, which contributes to a more faithful reconstruction of object structures. Second, to deal with artifacts introduced by stitching, we use a seam line method tailored to superpixels. The algorithm takes into account the feature similarity of neighborhood superpixels, including color difference, structure and entropy. We also consider the semantic information to avoid semantic misalignment. The optimal solution constrained by the cost functions is obtained under a graph model. The resulting stitched images exhibit improved naturalness. Extensive testing on common panorama stitching datasets is performed on the algorithm. Experimental results show that the proposed algorithm effectively mitigates artifacts, preserves the completeness of semantics and produces panoramic images with a subjective quality that is superior to that of alternative methods.

A multimodal material route planning problem considering key processes at work zones.

With the continuous development of large-scale engineering projects such as construction projects, relief support, and large-scale relocation in various countries, engineering logistics has attracted much attention. This paper addresses a multimodal material route planning problem (MMRPP), which considers the transportation of engineering material from suppliers to the work zones using multiple transport modes. Due to the overall relevance and technical complexity of engineering logistics, we introduce the key processes at work zones to generate a transport solution, which is more realistic for various real-life applications. We propose a multi-objective multimodal transport route planning model that minimizes the total transport cost and the total transport time. The model by using the ε - constraint method that transforms the objective function of minimizing total transportation cost into a constraint, resulting in obtaining pareto optimal solutions. This method makes up for the lack of existing research on the combination of both engineering logistics and multimodal transportation, after which the feasibility of the model and algorithm is verified by examples. The results show that the model solution with the introduction of the key processes at work zones produces more time-efficient and less time-consuming route planning results, and that the results obtained using the ε - constraint method are more reliable than the traditional methods for solving multi-objective planning problems and are more in line with the decision maker's needs.

Targeted protein degradation combined with PET imaging reveals the role of host PD-L1 in determining anti-PD-1 therapy efficacy.

PURPOSE: Immunohistochemical staining of programmed death-ligand 1 (PD-L1) in tumor biopsies acquired through invasive procedures is routinely employed in clinical practice to identify patients who are most likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy. Nevertheless, PD-L1 expression is observed in various cellular subsets within tumors and their microenvironments, including tumor cells, dendritic cells, and macrophages. The impact of PD-L1 expression across these different cell types on the responsiveness to anti-PD-1 treatment is yet to be fully understood. METHODS: We synthesized polymer-based lysosome-targeting chimeras (LYTACs) that incorporate both PD-L1-targeting motifs and liver cell-specific asialoglycoprotein receptor (ASGPR) recognition elements. Small-animal positron emission tomography (PET) imaging of PD-L1 expression was also conducted using a PD-L1-specific radiotracer 89Zr-αPD-L1/Fab. RESULTS: The PD-L1 LYTAC platform was capable of specifically degrading PD-L1 expressed on liver cancer cells through the lysosomal degradation pathway via ASGPR without impacting the PD-L1 expression on host cells. When coupled with whole-body PD-L1 PET imaging, our studies revealed that host cell PD-L1, rather than tumor cell PD-L1, is pivotal in the antitumor response to anti-PD-1 therapy in a mouse model of liver cancer. CONCLUSION: The LYTAC strategy, enhanced by PET imaging, has the potential to surmount the limitations of knockout mouse models and to provide a versatile approach for the selective degradation of target proteins in vivo. This could significantly aid in the investigation of the roles and mechanisms of protein functions associated with specific cell subsets in living subjects.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1.

The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

Temporal dynamics of chloroplast biogenesis revealed initiation of photosynthesis-related gene expression and protein complexes during alfalfa seed germination.

The chloroplast biogenesis occurs in cotyledon during alfalfa seed germination before true leaf formation, and is extremely important for the followed plant development and growth. In this study, we conducted a simulation of alfalfa seed germination in the soil by using tin foil and focused on 10 pivotal time points of chloroplast biogenesis in cotyledons before and after light exposure, which showed significant differences in multispectral images, and covered the whole process of chloroplast biogenesis from proplastid, etioplast to mature chloroplast. We revealed three phases that referred to the programmed involvements of photosynthesis promotion, ultrastructure maturity, transcriptomic expression, and protein complex construction, and observed distinct transcriptional expressions of genes from nuclear and chloroplast genomes. In phase I at dark germination before light exposure, chloroplast-encoded genes showed up-regulated expressions together with the importation of chloroplast proteins. In phase II for the first day after light exposure, nuclear-encoded genes' expressions were initiated at 2 h after light exposure (E2h), followed by swift assembly of chloroplast thylakoid membrane protein complexes, and roaring Fv/Fm and contents of chlorophyll a, chlorophyll b and carotenoid. The initiation at E2h was pronounced by the observation of gradual accumulation of single lamella, and facilitated the formation of granum stacks (thylakoid) at E8h in phase II. In phase III from the second day after light exposure, chloroplast became gradually complete with the fully established photosynthetic capacity. Altogether, our results layed a theoretical foundation for enhancing potential photosynthetic efficiency in alfalfa and related species.

Discrimination and hypertension among a diverse sample of racial and sexual minority men living with HIV: baseline findings of a longitudinal cohort study.

Racial and sexual orientation discrimination may exacerbate the double epidemic of hypertension (HTN) and HIV that affects men of color who have sex with men (MSM). This was a cross-sectional analysis of African American, Asian American, Native Hawaiian, or Pacific Islander (NHPI) MSM living with HIV (PLWH) cohort in Honolulu and Philadelphia. Racial and sexual orientation discrimination, stress, anxiety, and depression were measured with computer-assisted self-interview questionnaires (CASI). We examined the associations between racial and sexual orientation discrimination with hypertension measured both in the office and by 24-h ambulatory blood pressure monitoring (ABPM) using multivariable logistic regression. Sixty participants (60% African American, 18% Asian, and 22% NHPI) completed CASIs and 24-h ABPM. African American participants (80%) reported a higher rate of daily racial discrimination than Asian American (36%) and NHPI participants (17%, p < 0.001). Many participants (51%) reported daily sexual orientation discrimination. Sixty-six percent of participants had HTN by office measurement and 59% had HTN by 24-h ABPM measurement. Participants who experienced racial discrimination had greater odds of having office-measured HTN than those who did not, even after adjustment (Odds Ratio 5.0 (95% Confidence Interval [1.2-20.8], p = 0.03)). This association was not seen with 24-h ABPM. Hypertension was not associated with sexual orientation discrimination. In this cohort, MSM of color PLWH experience significant amounts of discrimination and HTN. Those who experienced racial discrimination had higher in-office blood pressure. This difference was not observed in 24-h APBM and future research is necessary to examine the long-term cardiovascular effects.

A facile method to fabricate sustainable bamboo ethanol lignin/carboxymethylcellulose films with efficient anti-ultraviolet and insulation properties.

Given the environmental concerns related to the non-degradability of conventional petroleum-based polymer films, the synthesis of biodegradable films utilizing natural polymers derived from biomass has emerged as a promising alternative, garnering significant attention in recent research endeavors. This research introduced an environmentally friendly and efficient method, utilizing extract liquid from the green ethanol pulping process as the solvent to completely dissolve carboxymethylcellulose into the film-forming liquid, and employing the solution pouring technique to successfully fabricate bamboo ethanol lignin/carboxymethylcellulose films (LCF). The findings revealed that the lignin content significantly influenced the LCF, endowing them with tunable mechanical properties, effective UV-blocking, and thermal insulation capabilities. With a lignin addition of 3.75 %, LCF-3.75 exhibited enhanced mechanical properties, characterized by a tensile strength of 19.4 MPa, along with superior UV-blocking efficiency, blocking 100 % of UVB and 99.81 % of UVA rays. Furthermore, relative to LCF-0, LCF-3.75 had been shown to possess enhanced hydrophobicity and thermal stability, culminating in the development of the composite films that showcased exceptional thermal insulation properties and biodegradability. The films not only harbored extensive application prospects as an anti-ultraviolet and heat-insulating glass films but also represented a potential avenue for the efficient utilization of lignin, thereby contributing to sustainable development.