Improving the Signal-to-Noise Ratio of Axial Displacement Measurements of Microspheres Based on Compound Digital Holography Microscopy Combined with the Reconstruction Centering Method.

In 3D microsphere tracking, unlike in-plane motion that can be measured directly by a microscope, axial displacements are resolved by optical interference or a diffraction model. As a result, the axial results are affected by the environmental noise. The immunity to environmental noise increases with measurement accuracy and the signal-to-noise ratio (SNR). In compound digital holography microscopy (CDHM)-based measurements, precise identification of the tracking marker is critical to ensuring measurement precision. The reconstruction centering method (RCM) was proposed to suppress the drawbacks caused by installation errors and, at the same time, improve the correct identification of the tracking marker. The reconstructed center is considered to be the center of the microsphere, rather than the center of imaging in conventional digital holographic microscopy. This method was verified by simulation of rays tracing through microspheres and axial moving experiments. The axial displacements of silica microspheres with diameters of 5 µm and 10 µm were tested by CDHM in combination with the RCM. As a result, the SNR of the proposed method was improved by around 30%. In addition, the method was successfully applied to axial displacement measurements of overlapped microspheres with a resolution of 2 nm.

Development of a dual point humidity sensor using POF based on twisted fiber structure.

The humidity has often been measured through a single point sensor. Where, the humidity could be varied at different locations as well as depending on environmental conditions. The present paper developed the dual point humidity measuring sensor by using a polymer optical fiber (POF) based on a single illuminating fiber. The sensor's basic structure is to twist two fibers and bend them at a certain radius. However, the dual point sensor is developed through the cascading of twisted micro bend (TMB-1 and TMB-2). The twisting of fibers couples the light from one fiber to another fiber through the side coupling method. An increase in the humidity level leads to a change in the reflective index, which helps to get variation in coupled light intensity. To measure the humidity, the dual point sensors are placed into the control humidity chamber at two random positions. The power reading variation is significantly linear when the humidity level increases from 30 to 80%. The sensor has a fast response of about 1 s and a recovery time of about 4 s. Furthermore, the chemical coating is applied to improve the sensor's sensitivity. Between 30 and 80% range of humidity, the both sensors of dual point TMB-1 and TMB-2 have appropriate sensitivity and detection limits, which is about 680.8 nW/% and 763.9 nW/% and 1.37% and 1.98%, respectively. To measure the humidity at variable positions, the present dual points humidity sensor is well-stable, easy, and straightforward, which uses a less expensive method.

A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

Efficient attribute-based strong designated verifier signature scheme based on elliptic curve cryptography.

In an attribute-based strong designated verifier signature, a signer who satisfies the access structure signs the message and assigns it to a verifier who satisfies the access structure to verify it, which enables fine-grained access control for signers and verifiers. Such signatures are used in scenarios where the identity of the signer needs to be protected, or where the public verifiability of the signature is avoided and only the designated recipient can verify the validity of the signature. To address the problem that the overall overhead of the traditional attribute-based strong designated verifier signature scheme is relatively large, an efficient attribute-based strong designated verifier signature scheme based on elliptic curve cryptography is proposed, as well as a security analysis of the new scheme given in the standard model under the difficulty of the elliptic curve discrete logarithm problem (ECDLP). On the one hand, the proposed scheme is based on elliptic curve cryptography and uses scalar multiplication on elliptic curves, which is computationally lighter, instead of bilinear pairing, which has a higher computational overhead in traditional attribute-based signature schemes. This reduces the computational overhead of signing and verification in the system, improves the efficiency of the system, and makes the scheme more suitable for resource-constrained cloud end-user scenarios. On the other hand, the proposed scheme uses LSSS (Linear Secret Sharing Schemes) access structure with stronger access policy expression, which is more efficient than the "And" gate or access tree access structure, making the computational efficiency of the proposed scheme meet the needs of resource-constrained cloud end-users.

Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients.

OBJECTIVES: This study sought to investigate the relationship between the systemic inflammatory response index (SIRI) and bone mineral density (BMD), osteoporosis, and future fracture risk in elderly hypertensive patients. METHODS: Elderly hypertensive patients (age ≥60 years) who attended our hospital between January 2021 and December 2023 and completed BMD screening were included in the study. Analyses were performed with multivariate logistic and linear regression. RESULTS: The multiple linear regression indicated that SIRI levels were significantly negatively correlated with lumbar 1 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 2 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 3 BMD (ß = -1.35, 95% CI: -0.23, -0.02), lumbar 4 BMD (ß = -0.11, 95% CI: -0.30, -0.10), femur neck BMD (ß = -0.11, 95% CI: -0.18, -0.05) and Ward's triangle BMD (ß = -0.12, 95% CI: -0.20, -0.05) among elderly hypertensive patients, after fully adjusting for confounders. Furthermore, we observed that SIRI was positively associated with future fracture risk in elderly hypertensive patients. Specifically, SIRI was associated with an increased risk of major osteoporotic fractures (ß = 0.33) and hip fractures (ß = 0.25). The logistic regression analysis indicated that there is an association between the SIRI level and an increased risk of osteoporosis (OR = 1.60, 95% CI = 1.37, 1.87), after fully adjusting for confounders. CONCLUSIONS: Our findings indicate a potential association between SIRI and BMD, osteoporosis, and the risk of future fractures in elderly hypertensive patients. However, further studies are warranted to confirm these findings.

The usage and costs of national drug price-negotiated anticancer medicines in a first-tier city in Northeast China: a study based on health insurance data.

BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.

Positive association between insulin resistance and fatty liver disease in psoriasis: evidence from a cross-sectional study.

Background: Fatty liver disease (FLD) is a common comorbidity of psoriasis and is often referred to as non-alcoholic fatty liver disease (NAFLD). However, the role of inflammation or insulin resistance (IR) in FLD is inconclusive. The study aims to explore whether FLD in psoriasis patients is more related to insulin resistance or systemic inflammation level. Methods: Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation Cohort, a prospective cohort that examines psoriasis characteristics in the Chinese population. IR was assessed using the triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) indicators. Systemic non-specific inflammation was assessed using the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII). Results: The analysis included a total of 647 patients. Subsequent logistic regression analysis revealed that NLR, dNLR, and SII were not significantly associated with FLD in psoriasis patients, while TyG and TyG-BMI showed significant associations with FLD. Subgroup analysis indicated that in the majority of subgroups, TyG and TyG-BMI were significantly associated with FLD, particularly TyG-BMI. Excluding individuals with methotrexate and acitretin resulted in consistent findings with the main analysis. Further analysis revealed a significantly higher diagnosis rate of metabolic-associated fatty liver disease (MAFLD) compared to NAFLD. Conclusions: Metabolic factors play a crucial role in FLD in patients with psoriasis, and TyG and TyG-BMI are potential predictors of FLD. Therefore, MAFLD can be recommend as a term to describe FLD in psoriasis patients. Trial registration: https://www.chictr.org.cn/showproj.html?proj=58256, identifier ChiCTR2000036186. A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population. Registered 31 August 2020.

Effect of Consultation Number on the Assessment and Treatment of Polycystic Ovary Syndrome.

Background: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare. Methods: This is a multicenter cross-sectional survey. Participants' basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0-50 people/yr, 50-200 people/yr, and >200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis. Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50-200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens. Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Study on the causal relationship between educational attainment and delirium: A two-sample Mendelian randomization study.

This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49-0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49-0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33-0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the "leave-one-out" analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.

Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non-Small Cell Lung Cancer.

We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18 and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding soluble (s) IL15, and further cytokine activated to induce PD-L1 expression. Our results show cryopreserved and thawed sIL15_TRACK NK cells had significantly improved cytotoxicity against non-small cell lung cancer (NSCLC) in vitro when compared to non-transduced (NT) NK cells, PD-L1+ NK cells lacking sIL15 expression (NT_TRACK NK), or NK cells expressing sIL15 without further cytokine activation (sIL15 NK cells). Intravenous injection of sIL15_TRACK NK cells into immunodeficient mice with NSCLC significantly slowed tumor growth and improved survival when compared to NT NK and sIL15 NK cells. The addition of the anti-PD-L1 atezolizumab further improved control of NSCLC growth by sIL15_TRACK NK cells in vivo. Moreover, a dose-dependent efficacy was assessed for sIL15_TRACK NK cells without observed toxicity. These experiments indicate that the administration of frozen, off-the-shelf allogeneic sIL15_TRACK NK cells is safe in preclinical models of human NSCLC and has potent antitumor activity without and with the administration of atezolizumab. A Phase I clinical trial modeled after this preclinical study using sIL15_TRACK NK cells alone or with atezolizumab for relapsed or refractory NSCLC is currently underway (NCT05334329).

Octave soliton microcombs in lithium niobate microresonators.

Soliton microcombs are regarded as an ideal platform for applications such as optical communications, optical sensing, low-noise microwave sources, optical atomic clocks, and frequency synthesizers. Many of these applications require a broad comb spectrum that covers an octave, essential for implementing the f - 2f self-referencing techniques. In this work, we have successfully generated an octave-spanning soliton microcomb based on a z-cut thin-film lithium niobate (TFLN) microresonator. This achievement is realized under on-chip optical pumping at 340 mW and through extensive research into the broadening of dual dispersive waves (DWs). Furthermore, the repetition rate of the octave soliton microcomb is accurately measured using an electro-optic comb generated by an x-cut TFLN racetrack microresonator. Our results represent a crucial step toward the realization of practical, integrated, and fully stabilized soliton microcomb systems based on TFLN.

Energy big data abnormal cluster detection method based on redundant convolution codec.

Due to the scattered distribution and poor clustering of abnormal clusters in energy big data, the ability to detect anomalies is poor. Therefore, a high-energy data anomaly clustering detection method based on redundant convolutional encoding is proposed. Quantitative analysis of the coupling characteristics of electrical thermal gas optical time series for multi energy users based on Copula function, and incorporating quantitative values into multi energy feature indicators to extract the energy consumption behavior characteristics of multi energy users. Utilize redundant convolutional codecs to recombine and structurally encode abnormal features of energy big data, and capture multi energy coupling time features using coupling time capsule layers. Then, coupling time features are synthesized through fully connected linear regression layers to generate anomalous clustering feature components, and the energy time series data is then transformed into feature values of the time series in three-dimensional space. Based on this, a comprehensive energy system and massive multi energy user energy big data anomaly clustering analysis are carried out to determine the optimal number of multi energy users. Then, based on linear layers, the electricity heat gas light load characteristic map of multi energy users is transformed into one-dimensional form, and an energy big data anomaly clustering detection model is constructed to complete anomaly detection. The simulation results show that the proposed method has excellent feature clustering performance, detection accuracy above 98.7%, fast convergence speed, and an error rate below 0.1, which has reliable application value.

Outcomes of Total Hip Arthroplasty Performed for HIV-Associated Osteonecrosis in China: A Retrospective Cohort Study.

BACKGROUND: In the post-epidemic era, Acquired Immune Deficiency Syndrome (AIDS) remains one of the most prevalent and detrimental infectious diseases worldwide. The incidence of osteonecrosis of the femoral head (ONFH) in AIDS patients is 100 times higher than that in healthy individuals. Although Total Hip Arthroplasty (THA) is ultimately necessary for most patients, there is still a dearth of evidence regarding its safety and efficacy in Chinese AIDS patients. METHODS: The clinical data of 49 patients who met the inclusion and exclusion criteria were retrospectively analyzed. Simultaneously, we categorized patients whose hemoglobin and albumin met a specific threshold as the optimized group and performed group comparisons. RESULTS: There are statistical differences in Harris score and VAS score pre- and post-operation, with a low overall complication rate. Notably, no disparities were observed between the optimized group and the partial optimized group in terms of overall conditions, laboratory examination indicators, severity of ONFH, surgical outcomes, surgical complications, pain perception or functional limitations. Furthermore, no correlation was found between CD4+ T lymphocytes and hemoglobin levels, albumin levels, white blood cell count, or platelet count. CONCLUSION: THA is safe and effective in Chinese AIDS patients with ONFH. However, optimal treatment has limited efficacy in AIDS patients undergoing THA for ONFH. The reconsideration and evaluation of the predictive value of CD4+ T lymphocytes for postoperative complications in joint replacement procedures is warranted.

Linker Mediated Electronic-State Manipulation of Conjugated Organic Polymers Enabling Highly Efficient Oxygen Reduction.

Conjugated polymers with tailorable composition and microarchitecture are propitious for modulating catalytic properties and deciphering inherent structure-performance relationships. Herein, we report a facile linker engineering strategy to manipulate the electronic states of metallophthalocyanine conjugated polymers and uncover the vital role of organic linkers in facilitating electrocatalytic oxygen reduction reaction (ORR). Specifically, a set of cobalt phthalocyanine conjugated polymers (CoPc-CPs) wrapped onto carbon nanotubes (denoted CNTs@CoPc-CPs) are judiciously crafted via in situ assembling square-planar cobalt tetraaminophthalocyanine (CoPc(NH2)4) with different linear aromatic dialdehyde-based organic linkers in the presence of CNTs. Intriguingly, upon varying the electronic characteristic of organic linkers from terephthalaldehyde (TA) to 2,5-thiophenedicarboxaldehyde (TDA) and then to thieno/thiophene-2,5-dicarboxaldehyde (bTDA), their corresponding CNTs@CoPc-CPs exhibit gradually improved electrocatalytic ORR performance. More importantly, theoretical calculations reveal that the charge transfer from CoPc units to electron-withdrawing linkers (i.e., TDA and bTDA) drives the delocalization of Co d-orbital electrons, thereby downshifting the Co d-band energy level. Accordingly, the active Co centers with more positive valence state exhibit optimized binding energy toward ORR-relevant intermediates and thus a balanced adsorption/desorption pathway that endows significant enhancement in electrocatalytic ORR. This work demonstrates a molecular-level engineering route for rationally designing efficient polymer catalysts and gaining insightful understanding of electrocatalytic mechanisms.

WWP2 protects against sepsis-induced cardiac injury through inhibiting cardiomyocyte ferroptosis.

Background and Objectives: Cardiac injury plays a critical role in contributing to the mortality associated with sepsis, a condition marked by various forms of programmed cell deaths. Previous studies hinted at the WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) involving in heart failure and endothelial injury. However, the precise implications of WWP2 in sepsis-induced cardiac injury, along with the underlying mechanisms, remain enigmatic. Methods: Sepsis induced cardiac injury were constructed by intraperitoneal injection of lipopolysaccharide. To discover the function of WWP2 during this process, we designed and performed loss/gain-of-function studies with cardiac-specific vectors and WWP2 knockout mice. Combination experiments were performed to investigate the relationship between WWP2 and downstream signaling in septic myocardium injury. Results: The protein level of WWP2 was downregulated in cardiomyocytes during sepsis. Cardiac-specific overexpression of WWP2 protected heart from sepsis induced mitochondrial oxidative stress, programmed cell death and cardiac injury, while knockdown or knockout of WWP2 exacerbated this process. The protective potency of WWP2 was predominantly linked to its ability to suppress cardiomyocyte ferroptosis rather than apoptosis. Mechanistically, our study revealed a direct interaction between WWP2 and acyl-CoA synthetase long-chain family member 4 (FACL4), through which WWP2 facilitated the ubiquitin-dependent degradation of FACL4. Notably, we observed a notable reduction in ferroptosis and cardiac injury within WWP2 knockout mice after FACL4 knockdown during sepsis. Conclusions: WWP2 assumes a critical role in safeguarding the heart against injury induced by sepsis via regulating FACL4 to inhibit LPS-induced cardiomyocytes ferroptosis.

Development of machine learning-based shelf-life prediction models for multiple marine fish species and construction of a real-time prediction platform.

At least 10 million tons of seafood products are spoiled or damaged during transportation or storage every year worldwide. Monitoring the freshness of seafood in real time has become especially important. In this study, four machine learning algorithms were used for the first time to develop a multi-objective model that can simultaneously predict the shelf-life of five marine fish species at multiple storage temperatures using 14 features such as species, temperature, total viable count, K-value, total volatile basic­nitrogen, sensory and E-nose-GC-Ms/Ms. as inputs. Among them, the radial basis function model performed the best, and the absolute errors of all test samples were <0.5. With the optimal model as the base layer, a real-time prediction platform was developed to meet the needs of practical applications. This study successfully realized multi-objective real-time prediction with accurate prediction results, providing scientific basis and technical support for food safety and quality.

8-Cl-Ado and 8-NH2-Ado synergize with venetoclax to target the methionine-MAT2A-SAM axis in acute myeloid leukemia.

Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes. Additionally, mass spectrometry analysis revealed that Venetoclax (VEN), a BCL-2 inhibitor recently approved by the FDA for AML treatment, significantly decreases the intracellular level of methionine in AML cells. Based on these findings, we hypothesized that combining 8CA or 8AA with VEN can efficiently target the Methionine-MAT2A-S-adenosyl-methionine (SAM) axis in AML. Our results demonstrate that VEN and 8CA/8AA synergistically decrease the SAM biosynthesis and effectively target AML cells both in vivo and in vitro. These findings suggest the promising potential of combining 8CA/8AA and VEN for AML treatment by inhibiting Methionine-MAT2A-SAM axis and provide a strong rationale for our recently activated clinical trial.

Tick species diversity and potential distribution alternation of dominant ticks under different climate scenarios in Xinjiang, China.

Ticks are a hematophagous parasite and a vector of pathogens for numerous human and animal diseases of significant importance. The expansion of tick distribution and the increased risk of tick-borne diseases due to global climate change necessitates further study of the spatial distribution trend of ticks and their potential influencing factors. This study constructed a dataset of tick species distribution in Xinjiang for 60 years based on literature database retrieval and historical data collection (January 1963-January 2023). The distribution data were extracted, corrected, and deduplicated. The dominant tick species were selected for analysis using the MaxEnt model to assess their potential distribution in different periods under the current and BCC-CSM2.MR mode scenarios. The results indicated that there are eight genera and 48 species of ticks in 108 cities and counties of Xinjiang, with Hyalomma asiaticum, Rhipicephalus turanicus, Dermacentor marginatus, and Haemaphysalis punctatus being the top four dominant species. The MaxEnt model analysis revealed that the suitability areas of the four dominant ticks were mainly distributed in the north of Xinjiang, in areas such as Altay and Tacheng Prefecture. Over the next four periods, the medium and high suitable areas within the potential distribution range of the four tick species will expand towards the northwest. Additionally, new suitability areas will emerge in Altay, Changji Hui Autonomous Prefecture, and other local areas. The 60-year tick dataset in this study provides a map of preliminary tick distribution in Xinjiang, with a diverse array of tick species and distribution patterns throughout the area. In addition, the MaxEnt model revealed the spatial change characteristics and future distribution trend of ticks in Xinjiang, which can provide an instrumental data reference for tick monitoring and tick-borne disease risk prediction not only in the region but also in other countries participating in the Belt and Road Initiative.