Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database.

OBJECTIVE: Zanubrutinib is a second-generation Bruton's tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events (AEs) associated with zanubrutinib based on the real-world data. DESIGN: A disproportionality analysis was performed to identify the potential zanubrutinib-related AEs. SETTING: The Food and Drug Administration AE Reporting System database from the fourth quarter of 2019 to the third quarter of 2023. MAIN OUTCOME MEASURES: The results of the disproportionality analyses were presented as reported ORs (RORs). When the lower limit of the 95% CI for the ROR is greater than 1 and the number of AE reports is≥3, it indicates that the preferred term (PT) may be a positive AE signal. RESULTS: A total of 846 AE reports with zanubrutinib as the primary suspect drug were obtained, with 2826 AEs. A total of 74 positive PT signals were detected across 18 system organ classes (SOCs). The most significant signal for SOC was 'blood and lymphatic system disorders' (ROR=2.8, 95% CI 2.3 to 3.3), while the most significant signal for PT was 'haemorrhage subcutaneous' (ROR=190.8, 95% CI 128.0 to 284.5). 13 unexpected off-label AEs were also observed, such as abnormal hair texture, skin discolouration, hypernatraemia, pericardial effusion and hypersomnia. The median time to onset of AEs associated with zanubrutinib was 51 days (IQR 13-192 days) and was consistent with the early failure model. In comparison with zanubrutinib monotherapy, the combination of zanubrutinib and rituximab therapy was linked to a higher risk of specific AEs, including myelosuppression, pneumonia, leucopenia, thrombocytopenia, abdominal pain, anaemia, pancytopenia and respiratory failure. Furthermore, the combination of zanubrutinib and chemotherapy increased the risk of several severe AEs, such as cardiac arrest, elevated blood lactate dehydrogenase levels and pancytopenia. CONCLUSIONS: The results of the analysis provided valuable insights into the safety profile of zanubrutinib-treated patients, which was helpful for clinical monitoring and identifying potential AEs related to zanubrutinib.

MicroRNAs in Hepatocellular Carcinoma: Insights into Regulatory Mechanisms, Clinical Significance, and Therapeutic Potential.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.

Development of Piophila megastigmata (Diptera: Piophilida) at seven constant temperatures.

In forensic entomology, the time-related growth and development of carrion insects allows for the estimation of the minimum postmortem interval (PMImin). Piophila megastigmata (Diptera: Piophilidae) is of great significance in estimating PMImin in the late stage of corpse decay. In this paper, the development of P. megastigmata was investigated under the seven constant temperatures of 16-34 °C. The total development time at each temperature was 970.38, 824.50, 593.13, 498.25, 392.00, 385.63 and 405.87 h, respectively. The isomorphen diagram shows the trend of development during different developmental stages at different temperatures. By using a revised linear regression model, the estimated lower lethal developmental thresholds (TL) and thermal summation constant (K) were found to be 10.57 °C and 6936.78 degree hours, respectively. According to a nonlinear model, the TL, upper lethal developmental thresholds (TH), and intrinsic optimum temperature (TΦ) were determined to be 7.53, 34.68, and20.43 °C, respectively. Also, logistic function and an isomegalen diagram were constructed according to the continuous changes in larval body length, and illustrates the time required to develop to a certain length at different temperatures. The obtained results offer crucial fundamental developmental information regarding P. megastigmata, which can be applied in PMImin estimation.

Development and age estimation of the intrapuparial period of Phormia regina (Diptera: Calliphoridae) for postmortem interval estimation.

Phormia regina (Meigen, 1826; Diptera: Calliphoridae) is a Holarctic species that rapidly colonizes carcasses and has been used as an indicator for determining the minimum postmortem interval. However, studies using morphological methods to estimate the intrapuparial age of P. regina are lacking. In this study, morphological changes within the puparium were observed under a stereomicroscope at 7 constant temperatures ranging from 16 °C to 34 °C. The intrapuparial period was categorized into 12 substages. Morphological indicators, including compound eyes, mouthparts, antennae, thorax, legs, wings, and abdomen, were recorded in detail. The observed morphological changes were divided into 6-10 substages, and the duration of each substage was also recorded in detail. The results of this study provide primary data for using the intrapuparial morphology of P. regina when pupae are collected at a crime scene and estimating the minimum postmortem interval.

Drug-Induced Gynecomastia: Data Mining and Analysis of the FDA Adverse Event Reporting System Database.

Purpose: Drug-induced gynecomastia significantly affects patient health and quality of life. This study aimed to perform an exploratory analysis of gynecomastia reports and the most commonly associated medications within the FAERS database. Patients and Methods: A comprehensive analysis of the FAERS from January 2004 to December 2023 was conducted. Disproportionality analysis and subsequent sensitivity analysis were performed to identify drugs potentially associated with gynecomastia, utilizing the reported odds ratio (ROR). Logistic regression analysis was employed to assess potential risk factors. The Weibull shape parameter (WSP) test was used to assess the time-to-onset characteristics of the top drugs associated with gynecomastia. Results: The study identified 30,265 cases of gynecomastia, primarily associated with nervous system drugs, accounting for 85.50% of cases. Notably, risperidone accounted for 80.81% of the total cases. Among the 165 agents with ≥ 5 cases of gynecomastia, the strongest signals were exhibited by risperidone (ROR 602.38, 95% CI 585.07-620.20), dutasteride (ROR 17.18, 95% CI 15.55-18.89), spironolactone (ROR 15.8, 95% CI 13.99-17.83), and paliperidone (ROR 7.16, 95% CI 6.55-7.84). In the sensitivity analysis of disproportionality, unexpected associations were observed, such as montelukast (n = 21, ROR 1.94, 95% CI 1.26-2.98). The logistic regression analysis indicated that the risk of risperidone-induced gynecomastia was significantly lower in adults compared to pediatric patients (OR 0.12, 95% CI 0.09-0.15) and in patients with higher body weight than in those with lower body weight (OR 5.24, 95% CI 3.62-7.76). The WSP test showed that gynecomastia induced by most of the top 10 common agents tends to occur in an early failure mode. Conclusion: The rankings and signal strengths of drugs associated with gynecomastia were extracted from the FAERS. The age distribution and time-to-onset distribution of the top 10 drugs linked to gynecomastia were investigated, which can facilitate accurate clinical recognition of drug-induced gynecomastia.

cost-effectiveness of aumolertinib as first-line treatment for EGFR-mutated advanced nonsmall-cell lung cancer.

Aim: To evaluate the cost-effectiveness of aumolertinib as the epidermal growth factor receptor-mutated advanced nonsmall-cell lung cancer first-line treatment from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the AENEAS trial. Only direct medical costs were considered in the model. Utilities were obtained from published literature. Sensitivity and scenario analyses were performed to explore the robustness of the model.Results: Compared with gefitinib, aumolertinib yielded an additional 0.941 expected life-years and 0.692 quality-adjusted life-years (QALYs), with an incremental cost of $18,855.55 over a 20-year time horizon. The incremental cost-effectiveness ratios were $20,051.67/life-year and $27,272.29/QALY, that below the willing-to-pay threshold of $38,223.34/QALY.Conclusion: Aumolertinib was a cost-effective alternative first-line treatment for patients with epidermal growth factor receptor-positive advanced nonsmall-cell lung cancer in China.

What is this article about? This study assesses the costs and health outcomes associated with aumolertinib therapy for Chinese patients diagnosed with advanced or metastatic nonsmall cell lung cancer (NSCLC). Aumolertinib therapy is a specific type of medication used to treat a certain type of lung cancer called nonsmall cell lung cancer. It is a newer treatment that targets certain genetic changes in the cancer cells.How was this done? The costs and treatment benefits were estimated using data from the AENEAS trial, provincial medical cost lists and previously published studies. A Markov model was developed to simulate disease progression. Provincial Medical Cost Lists are official lists maintained by different provincial governments in China that specify the drugs and their prices that are covered by the public healthcare system. A Markov Model is a mathematical tool used to predict how a disease might progress over time. It is like a simulation where the possible outcomes of the disease are analyzed, helping to understand the likely course of the disease and how different treatments might affect it.What were the results? The cost of treatment with aumolertinib for Chinese patients with advanced or metastatic NSCLC was considered to be acceptable based on the benefits it provides.What do the study results mean? The results suggest that aumolertinib is a cost-effective treatment for patients with advanced or metastatic NSCLC in China.

Immune checkpoint inhibitors as the second-line treatment for advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis based on network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

Elevation Influences Belowground Biomass Proportion in Forests by Affecting Climatic Factors, Soil Nutrients and Key Leaf Traits.

Forest biomass allocation is a direct manifestation of biological adaptation to environmental changes. Studying the distribution patterns of forest biomass along elevational gradients is ecologically significant for understanding the specific impacts of global change on plant resource allocation strategies. While aboveground biomass has been extensively studied, research on belowground biomass remains relatively limited. Furthermore, the patterns and driving factors of the belowground biomass proportion (BGBP) along elevational gradients are still unclear. In this study, we investigated the specific influences of climatic factors, soil nutrients, and key leaf traits on the elevational pattern of BGBP using data from 926 forests at 94 sites across China. In this study, BGBP data were calculated from the root biomass to the depth of 50 cm. Our findings indicate considerable variability in forest BGBP at a macro scale, showing a significant increasing trend along elevational gradients (p < 0.01). BGBP significantly decreases with increasing temperature and precipitation and increases with annual mean evapotranspiration (MAE) (p < 0.01). It decreases significantly with increasing soil phosphorus content and increases with soil pH (p < 0.01). Key leaf traits (leaf nitrogen (LN) and leaf phosphorus (LP)) are positively correlated with BGBP. Climatic factors (R2 = 0.46) have the strongest explanatory power for the variation in BGBP along elevations, while soil factors (R2 = 0.10) and key leaf traits (R2 = 0.08) also play significant roles. Elevation impacts BGBP directly and also indirectly through influencing such as climate conditions, soil nutrient availability, and key leaf traits, with direct effects being more pronounced than indirect effects. This study reveals the patterns and controlling factors of forests' BGBP along elevational gradients, providing vital ecological insights into the impact of global change on plant resource allocation strategies and offering scientific guidance for ecosystem management and conservation.

Climate Factors Influence Above- and Belowground Biomass Allocations in Alpine Meadows and Desert Steppes through Alterations in Soil Nutrient Availability.

Biomass is a direct reflection of community productivity, and the allocation of aboveground and belowground biomass is a survival strategy formed by the long-term adaptation of plants to environmental changes. However, under global changes, the patterns of aboveground-belowground biomass allocations and their controlling factors in different types of grasslands are still unclear. Based on the biomass data of 182 grasslands, including 17 alpine meadows (AMs) and 21 desert steppes (DSs), this study investigates the spatial distribution of the belowground biomass allocation proportion (BGBP) in different types of grasslands and their main controlling factors. The research results show that the BGBP of AMs is significantly higher than that of DSs (p < 0.05). The BGBP of AMs significantly decreases with increasing mean annual temperature (MAT) and mean annual precipitation (MAP) (p < 0.05), while it significantly increases with increasing soil nitrogen content (N), soil phosphorus content (P), and soil pH (p < 0.05). The BGBP of DSs significantly decreases with increasing MAP (p < 0.05), while it significantly increases with increasing soil phosphorus content (P) and soil pH (p < 0.05). The random forest model indicates that soil pH is the most important factor affecting the BGBP of both AMs and DSs. Climate-related factors were identified as key drivers shaping the spatial distribution patterns of BGBP by exerting an influence on soil nutrient availability. Climate and soil factors exert influences not only on grassland biomass allocation directly, but also indirectly by impacting the availability of soil nutrients.

Modeling and analyzing self-resistance of connected automated vehicular platoons under different cyberattack injection modes.

The high-level integration and interaction between the information flow at the cyber layer and the physical subjects at the vehicular layer enables the connected automated vehicles (CAVs) to achieve rapid, cooperative and shared travel. However, the cyber layer is challenged by malicious attacks and the shortage of communication resources, which makes the vehicular layer suffer from system nonlinearity, disturbance randomness and behavior uncertainty, thus interfering with the stable operation of the platoon. So far, scholars usually adopt the method of assuming or improving the car-following model to explore the platoon behavior and the defense mechanism in cyberattacks, but they have not considered whether the model itself has disturbance and impact on cyberattack defenses. In other words, it is still being determined whether the car-following model designed can be fully applicable to such cyberattacks. To provide a theoretical basis for vehicular layer modeling, it is necessary to comprehend the self-resistance of different car-following models faced on various cyberattacks. First, we review the car-following models adopted on the vehicular layer in cyberattacks, involving traffic engineering, physical statistics, and platoon dynamics. Based on the review, we divide the malicious attacks faced by the cyber layer into explicit attacks and implicit attacks. Second, we develop a cooperative generalized force model (CGFM), which combines and unifies the r-predecessors following communication topology. The proposed models, labeled the vulnerable cooperative intelligent driver model (VCIDM), the vulnerable cooperative optimal velocity model (VCOVM), and the vulnerable cooperative platoon dynamics model (VCPDM), incorporate the CGFM model and assorted cyberattack injection modes to explain the cyberattack effects on the platoon self-resistance capability. Upon the described models, we provide six indicators in three dimensions from the basic traffic element, including drivers, vehicles, and environment. These indicators illustrate driver tolerance, vehicle adaptability, and environmental resistance when a platoon faces attacks such as bogus information, replay/delay, and communication interruption. We arrange and reorganize the car-following models and the cyberattack injection modes to complete the research on the self-resistance capability of the platoon, which has positive research value and practical significance for enhancing the endogenous security at the vehicular layer and improving the intrusion tolerability at the cyber layer.

Development of Megaselia scalaris at constant temperatures and its significance in estimating the time of death.

Megaselia scalaris (Schmitz, 1938) (Diptera: Phoridae) is a common insect in forensic science that is frequently found in indoor cases, particularly on corpses in closed environments. Although this species is useful for estimating the minimum postmortem interval (PMImin) in the absence of Calliphoridae, there is a lack of data on its development in China. Herein, we studied the development of M. scalaris exposed to seven constant temperatures ranging from 16 to 34 °C. The mean (± SD) developmental durations of M. scalaris from egg to adult stage at 16, 19, 22, 25, 28, 31, and 34 °C were 1486.9 ± 75.3, 823.7 ± 42.8, 448.2 ± 59.8, 417.7 ± 19.7, 297.2 ± 27.3, 272.9 ± 10.4, and 253.0 ± 5.0 h, respectively. The mean (± SE) lower developmental threshold temperature (TL) and the thermal summation constant (K) were determined by a linear model as 12.69 ± 0.3 °C and 4965.8 ± 227.9-degree hours, respectively. A nonlinear model estimated the lower developmental threshold temperature, intrinsic optimum temperature, and upper lethal developmental threshold temperature as 14.58, 21.00, and 34.15 °C, respectively. We established three development models to estimate the age of the immature insect, namely the isomegalen diagram, isomorphen diagram, and thermal summation model. In addition, a regression analysis of the relationship between body length and total development time from hatching to pupariation was performed. Our findings provide a basis for applications of M. scalaris in PMImin estimations.

A novel mathematical model and application software for estimating the age of necrophagous fly larvae.

The change in larval body length of necrophagous flies during their development is a key indicator for estimating larval age. However, existing forensic entomological models have limitations in this regard. In this study, a logistic algorithm was used to establish a general model for estimating the minimum postmortem interval (PMImin) using larval body length. The new model was used to simulate the relationship between larval body length and developmental time of eight species of necrophagous flies. The model parameters of body length variation with developmental time of the different species were calculated. Computer software was developed based on the established logistic model. The advantage of the new model is that each parameter has a biological meaning and can be used to estimate the age of larvae at any temperature and any larval body length. Cross-validation of the model showed that the overall mean accuracy of the fitted growth curves for the eight necrophagous fly larvae was 82.7%, the mean accuracy of age extrapolations for seven necrophagous fly species ranged from 76.8% to 92.9%, while the accuracy of age extrapolations for only one species was lower (i.e., 63.3%). This study provides a new method to estimate the PMImin based on larval body length, and the developed computer software will facilitate its application in forensic entomology.

Developmental Indicators of Chrysomya nigripes Aubertin under Different Constant Temperature Conditions and an Application Case for Estimating the PMImin.

Chrysomya nigripes Aubertin, 1932, is a Calliphoridae species that colonize the carcass after the bloat phase and remains for long periods. Some early sarcosaprophagous insects complete one generation of development and are no longer associated with the corpse and surrounding environment, while C. nigripes larvae and pupae remain, providing a basis for the estimation of the minimum postmortem interval (PMImin) for highly decomposed or skeletonized carcasses. However, data on the growth and development of this species are not yet complete. As a result, we studied the developmental patterns of C. nigripes at eight constant temperatures ranging from 16-37 °C and constructed various developmental models, including the isomorphen diagram, isomegalen diagram, linear thermal summation model, nonlinear thermodynamic Optim SSI model, and logistic regression model. Chrysomya nigripes could not complete the entire developmental process at 16 °C, although it could be completed at other temperatures. The mean developmental times (±SD) of C. nigripes from egg to adult at 19 °C, 22 °C, 25 °C, 28 °C, 31 °C, 34 °C, and 37 °C were 644.9 ± 36.8 h, 422.9 ± 20.1 h, 323.1 ± 13.9 h, 246.6 ± 11.2 h, 202.5 ± 1.8 h, 191.5 ± 3.8 h, and 191.8 ± 2.0 h, respectively. The thermal summation constant (K) and lower critical thermal threshold (TL) derived from the linear thermal summation models were 4083.00 ± 293.39 degree hours and 12.52 ± 0.83 °C, respectively. In addition, TL, intrinsic optimum temperature (TΦ), and upper critical thermal threshold (TH) estimated by the optimized nonlinear thermodynamic Optim SSI model were 15.76 °C, 24.88 °C, and 38.15 °C, respectively. This study provides more comprehensive developmental data of C. nigripes for PMImin estimation.

A global perspective of forensic entomology case reports from 1935 to 2022.

Forensic entomology case reports are the product of rapid development in the field, the widespread acceptance of the science and the application of forensic entomological knowledge. In this study, we retrospectively summarized information derived from 307 forensic entomology case reports from 1935 to 2022 from a global perspective. Our checklist of relevant information included insect species, specific indoor or outdoor preferences, preferred temperatures, and stages of body decomposition. Finally, a concept and calculation method for postmortem interval (PMI) estimation accuracy was proposed. There were 232 cases using insect developmental data and 28 cases using succession patterns to estimate PMI. A total of 146 species of insects were involved in the cases, of which 62.3% were Diptera and 37.7% were Coleoptera. Postmortem intervals were estimated from eggs in 4 cases, larvae in 180 cases, pupae in 45 cases, and puparia in 38 cases. The majority of cases were from June to October, and the average number of species mentioned in the cases was more at 15-30 °C. Considering the standardization of application, in the majority of cases, insect evidence was collected by other personnel and sent to forensic entomologists, there was a delay in the sampling, and the scene or meteorological data were directly used without correcting. Our data shows that there are still many shortcomings in the universality and standardization of forensic entomology in its practical application.

Climate factors affect forest biomass allocation by altering soil nutrient availability and leaf traits.

Biomass in forests sequesters substantial amounts of carbon; although the contribution of aboveground biomass has been extensively studied, the contribution of belowground biomass remains understudied. Investigating the forest biomass allocation is crucial for understanding the impacts of global change on carbon allocation and cycling. Moreover, the question of how climate factors affect biomass allocation in natural and planted forests remains unresolved. Here, we addressed this question by collecting data from 384 planted forests and 541 natural forests in China. We evaluated the direct and indirect effects of climate factors on the belowground biomass proportion (BGBP). The average BGBP was 31.09% in natural forests and was significantly higher (38.75%) in planted forests. Furthermore, we observed a significant decrease in BGBP with increasing temperature and precipitation. Climate factors, particularly those affecting soil factors, such as pH, strongly affected the BGBP in natural and planted forests. Based on our results, we propose that future studies should consider the effects of forest type (natural or planted) and soil factors on BGBP.

Surgical selection and regional lymph node dissection for stage I second primary lung cancer patients following surgery for stage I first primary lung cancer.

Introduction: Studies investigating surgery for second primary non-small cell lung cancer (SP) patients are rare. The aim of this study was to explore the effects of surgical methods and regional lymph node (LN) dissection on lung cancer-specific mortality (LCSM) in stage I SP patients following surgery for stage I first primary non-small cell lung cancer (FP). Methods: Data on patients diagnosed with stage I SP after surgery for stage I FP were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative incidence function (CIF) curves, a competing risk model and propensity score matching (PSM) were adopted to compare the LCSM among different subgroups (including surgery and regional LN dissection). Results: A total of 238 stage I SP patients were extracted from the SEER database. Overall, the 5-year LCSM rate was 29.8% (CI: 23.1%-36.5%) for the whole cohort. Both before and after PSM, lobectomy had a similar LCSM incidence as sublobectomy, and ≥4 regional LN dissections had a significantly lower LCSM incidence than 1~3 regional LN dissections.In addition, patients who underwent 1~3 regional LN dissections had a comparable incidence of LCSM to those without LN dissections. Discussion: Stage I SP patients tended to gain more survival benefits when surgeons dissect ≥4 regional LNs. Allowing for the comparable LCSM incidence of sublobectomy to lobectomy, sublobectomy may be a reasonable choice for thoracic surgeons when performing surgery for these patients.

Temperature-Dependent Development of Nitidula rufipes (Linnaeus, 1767) (Coleoptera: Nitidulidae) and Its Significance in Estimating Minimum Postmortem Interval.

Coleoptera, including the family Nitidulidae, are valuable for estimating long-term postmortem intervals in the late stage of body decomposition. This study showed that, under seven constant temperatures of 16, 19, 22, 25, 28, 31, and 34 °C, the developmental durations of Nitidula rufipes (Linnaeus, 1767) from oviposition to eclosion were 71.0 ± 4.4, 52.9 ± 4.1, 40.1 ± 3.4, 30.1 ± 2.1, 24.2 ± 2.0, 21.0 ±2.3, and 20.8 ± 2.4 days, respectively. The morphological indexes of body length, the widths of the head capsules, and the distance between the urogomphi of the larvae were measured in vivo. The regression model between larval body length and developmental durations was simulated for larval aging, and the head capsule width and the distance between the urogomphi at different instars were cluster-analyzed for instar discrimination. Based on the developmental durations, larval body length and thermal summation data were obtained, and the isomorphen diagram, isomegalen diagram, linear thermal summation models, and curvilinear Optim SSI models were established. The lower developmental threshold and thermal summation constant of N. rufipes evaluated by the linear thermal summation models were 9.65 ± 0.62 °C and 471.40 ± 25.46 degree days, respectively. The lower developmental thresholds, intrinsic optimum temperature, and upper lethal developmental threshold obtained by Optim SSI models were 10.12, 24.15, and 36.00 °C, respectively. The study of the immature stages of N. rufipes can provide preliminary basic developmental data for the estimation of minimum postmortem interval (PMImin). However, more extensive studies are needed on the effects of constant and fluctuating temperatures on the development of N. rufipes.

Estimating the intra-puparial period of Hydrotaea spinigera (Stein,1910) (Diptera: Muscidae) with morphological and gene expression changes.

Hydrotaea spinigera (Stein, 1910) (Diptera: Muscidae) is a forensically important sarcosaprophagous species widely distributed throughout the Oriental and Australasian regions. At the advanced decomposition stage or the skeletonize stage, the immature stages of H. spinigera, especially the pupae, can still be found in large quantities and could be used as important indicators to estimate the minimum postmortem interval (PMImin). However, there have been no studies on the intra-puparial period of this species. Herein, we studied morphological and differential gene expression changes during the intra-puparial development of H. spinigera, aiming to accurately estimate the intra-puparial age of H. spinigera. The intra-puparial morphological changes of H. spinigera were observed at seven constant temperatures ranging from 16 °C to 34 °C and divided into 12 sub-stages. Structures that could be used to estimate the intra-puparial age, such as compound eyes, mouthparts, antennae, thorax, legs, wings, and abdomen, were observed in detail, and the developmental process of each structure was divided into 5 to 10 stages. The time range of each sub-stage, or when a structure appeared, was recorded. For the gene expression section, the most suitable reference genes were screened by geNorm, NormFinder, BestKeeper, and ΔCt methods. Based on the selected reference genes, real-time quantitative PCR (RT qPCR) was used to detect the expression changes of the white and hsp90 genes with developmental time at 19 °C, 25 °C, and 31 °C. Results showed that the trend of hsp90 gene expression under different temperatures was not consistent, while white genes exhibited regular changes during development, and could thus be used for age estimation of H. spinigera. This study provides an important basis for forensic entomology to use morphological and differential gene expression for estimating the age of H. spinigera during the intra-puparial period. Moreover, the combination of the two methods can produce a more accurate minimum postmortem interval (PMImin) estimate compared to when each method is used separately.

Time Effects of Global Change on Forest Productivity in China from 2001 to 2017.

With global warming, the concentrations of fine particulate matter (PM2.5) and greenhouse gases, such as CO2, are increasing. However, it is still unknown whether these increases will affect vegetation productivity. Exploring the impacts of global warming on net primary productivity (NPP) will help us understand how ecosystem function responds to climate change in China. Using the Carnegie-Ames-Stanford Approach (CASA) ecosystem model based on remote sensing, we investigated the spatiotemporal changes in NPP across 1137 sites in China from 2001 to 2017. Our results revealed that: (1) Mean Annual Temperature (MAT) and Mean Annual Precipitation (MAP) were significantly positively correlated with NPP (p < 0.01), while PM2.5 concentration and CO2 emissions were significantly negatively correlated with NPP (p < 0.01). (2) The positive correlation between temperature, rainfall and NPP gradually weakened over time, while the negative correlation between PM2.5 concentration, CO2 emissions and NPP gradually strengthened over time. (3) High levels of PM2.5 concentration and CO2 emissions had negative effects on NPP, while high levels of MAT and MAP had positive effects on NPP.

Effects of Soil Nutrients on Plant Nutrient Traits in Natural Pinus tabuliformis Forests.

In light of global warming, the interaction between plant nutrient traits and soil nutrients is still unclear. Plant nutrient traits (e.g., N and P) and their stoichiometric relationships (N/P ratio) are essential for plant growth and reproduction. However, the specific role of soil nutrients in driving variation in plant nutrient traits remains poorly understood. Fifty natural Pinus tabuliformis forests were used as the research object to clarify the interaction between plant nutrient traits and soil nutrients. We show that: (1) The Nmass, Pmass and N/P ratios of leaves were significantly higher than those of roots. The N/P ratio of both leaves and roots was less than 14. (2) Leaf nutrient traits showed diverse relationship patterns with root nutrient traits throughout the growing period. Significant changes were found in root nutrient PC2 (the second principal component of root nutrient traits) and leaf nutrient PC1 (the first principal component of leaf traits), and non-significant changes were found in other relationships between leaf and root traits (p > 0.05). Root nutrient traits explained 36.4% of the variance in leaf nutrient traits. (3) With the increase in soil nutrient PC2 (related to N), leaf PC2 (related to N) showed a significant trend of first decreasing and then increasing (p < 0.05). Only the soil Nmass was significantly correlated with the leaf Nmass (p < 0.05), which demonstrated that the growth and survival of Pinus tabuliformis forests were mainly affected by N-limitation.