Implementation of antibody-drug conjugates in HER2-positive solid cancers: Recent advances and future directions.

In recent decades, there has been a surge in the approval of monoclonal antibodies for treating a wide range of hematological and solid malignancies. These antibodies exhibit exceptional precision in targeting the surface antigens of tumors, heralding a groundbreaking approach to cancer therapy. Nevertheless, monoclonal antibodies alone do not show sufficient lethality against cancerous cells compared to chemotherapy. Consequently, a new class of anti-tumor medications, known as antibody-drug conjugates (ADCs), has been developed to bridge the divide between monoclonal antibodies and cytotoxic drugs, enhancing their therapeutic potential. ADCs are chemically synthesized by binding tumor-targeting monoclonal antibodies with cytotoxic payloads through linkers that are susceptible to cleavage by intracellular proteases. They combined the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity and boasting superior lethality over standalone targeted drugs. The human epidermal growth factor receptor (HER) family, which encompasses HER1 (also known as EGFR), HER2, HER3, and HER4, plays a key role in regulating cellular proliferation, survival, differentiation, and migration. HER2 overexpression in various tumors is one of the most frequently targeted antigens for ADC therapy in HER2-positive cancers. HER2-directed ADCs have emerged as highly promising treatment modalities for patients with HER2-positive cancers. This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.

Advancements in elucidating the pathogenesis of actinic keratosis: present state and future prospects.

Solar keratosis, also known as actinic keratosis (AK), is becoming increasingly prevalent. It is a benign tumor that develops in the epidermis. Individuals with AK typically exhibit irregular, red, scaly bumps or patches as a result of prolonged exposure to UV rays. These growths primarily appear on sun-exposed areas of the skin such as the face, scalp, and hands. Presently, dermatologists are actively studying AK due to its rising incidence rate in the United States. However, the underlying causes of AK remain poorly understood. Previous research has indicated that the onset of AK involves various mechanisms including UV ray-induced inflammation, oxidative stress, complex mutagenesis, resulting immunosuppression, inhibited apoptosis, dysregulated cell cycle, altered cell proliferation, tissue remodeling, and human papillomavirus (HPV) infection. AK can develop in three ways: spontaneous regression, persistence, or progression into invasive cutaneous squamous cell carcinoma (cSCC). Multiple risk factors and diverse signaling pathways collectively contribute to its complex pathogenesis. To mitigate the risk of cancerous changes associated with long-term UV radiation exposure, prompt identification, management, and prevention of AK are crucial. The objective of this review is to elucidate the primary mechanisms underlying AK malignancy and identify potential treatment targets for dermatologists in clinical settings.

Low-Temperature Synthesis of WSe2 by the Selenization Process under Ultrahigh Vacuum for BEOL Compatible Reconfigurable Neurons.

Low-temperature large-area growth of two-dimensional (2D) transition-metal dichalcogenides (TMDs) is critical for their integration with silicon chips. Especially, if the growth temperatures can be lowered below the back-end-of-line (BEOL) processing temperatures, the Si transistors can interface with 2D devices (in the back end) to enable high-density heterogeneous circuits. Such configurations are particularly useful for neuromorphic computing applications where a dense network of neurons interacts to compute the output. In this work, we present low-temperature synthesis (400 °C) of 2D tungsten diselenide (WSe2) via the selenization of the W film under ultrahigh vacuum (UHV) conditions. This simple yet effective process yields large-area, homogeneous films of 2D TMDs, as confirmed by several characterization techniques, including reflection high-energy electron diffraction, atomic force microscopy, transmission electron microscopy, and different spectroscopy methods. Memristors fabricated using the grown WSe2 film are leveraged to realize a novel compact neuron circuit that can be reconfigured to enable homeostasis.

Cervical cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with England and India based on the global burden of disease study 2019.

Background: Cervical cancer is the fourth highest incidence of malignancy in the world and a common cause of cancer death in women. We assessed the trends of incidence and mortality and disability-adjusted life year (DALY) in China, England and India from 1990 to 2030. Method: Data were obtained from the Global Burden of Disease (GBD) database. We collected the number and rate of incidence, death and DALY from 1990 to 2019 and calculated the estimated annual percentage change (EAPC). Further analysis was carried out by ages and years. We also collected attributable risk factors to cervical cancer. Finally, we utilized the Bayesian Age-Period-Cohort (BAPC) model to forecast trends in the rate of age-standardized incidence (ASIR) and age-standardized death (ASDR) the for the next decade. Result: Globally, the incidence of cervical cancer cases increased from 335,641.56 in 1990 to 565,540.89 in 2019. In 2019, the ASIR and ASDR of cervical cancer were higher than those of India but lower than those of England. Furthermore, unsafe sex and smoking emerge as prominent risk factors for cervical cancer. Over the next decade, ASIR and ASDR are expected to decline in China and England, while India's ASIR is still on an upward trend and ASDR is on a downward trend. Conclusion: The epidemiological data of cervical cancer in these three countries reflects the influence of different stages of development and healthcare systems. Trends over the next decade suggest that China and India still face a huge burden of cervical cancer. When England has made significant progress, China and India need to take more measures to improve the prevention and control of cervical cancer.

Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses.

Background: Cervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated. Methods: We utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes. Results: Through our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator-the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines. Conclusion: This study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches.

The Characteristics of the Root-Zone Soil's Biological Properties and Microbial Community Structure in Grafted Star Anise Plantations.

Extensive management seriously affects the output, quality, and sustainable development of star anise, and grafting is commonly used to improve its production and quality. Although many studies have explored the effects of grafting on soil microorganisms for other plants, there is a lack of research on aromatic plants, especially on the soil ecosystems of star anise plantations. The effect of grafting star anise on the soil's biological characteristics and microbial composition remains unclear. The soil's enzyme activities, soil microbial biomass, and microbial community composition in grafted and non-grafted star anise plantations in Guangxi, China were studied using high-throughput sequencing technology. The results showed that the microbial biomass carbon and phosphorus contents in the soils of grafted star anise were significantly lower and the phosphatase activity was significantly higher than in the soils of non-grafted star anise. In comparison with the soils of non-grafted star anise plantations, the proportions of Proteobacteria, Acidobacteria, Actinobacteria, and WPS-2 decreased and the proportions of Chloroflexi, Planctomycetes, and Verrucomicrobia increased in the grafted star anise plantations. Meanwhile, Bacteroidetes was a dominant bacterial phylum unique to the soil of the grafted star anise plantations. Moreover, the proportions of Ascomycota and Basidiomycota increased and the proportions of Mortierellomycota and unclassified_k_Fungi decreased in the soils of the grafted star anise plantations. Furthermore, Basidiomycota and Rozellomycota had significant dominance in the grafted star anise plantations. In general, grafting can improve soil fertility and maintain soil health by promoting soil nutrient cycling and increasing the soil's microbial diversity.

Enrichment of Phosphopeptides Based on Zirconium Phthalocyanine-Modified Magnetic Nanoparticles.

Highly selective extraction of phosphopeptides is necessary before mass spectrometry (MS) analysis. Herein, zirconium phthalocyanine-modified magnetic nanoparticles were prepared through a simple method. The Fe-O groups on Fe3O4 and the zirconium ions on phthalocyanine had a strong affinity for phosphopeptides based on immobilized metal ion affinity chromatography (IMAC). The enrichment platform exhibited low detection limit (0.01 fmol), high selectivity (α-/ß-casein/bovine serum albumin, 1/1/5000), good reusability (10 circles), and recovery (91.1 ± 1.1%) toward phosphopeptides. Nonfat milk, human serum, saliva, and A549 cell lysate were employed as actual samples to assess the applicability of the enrichment protocol. Metallo-phthalocyanine will be a competitive compound for designing highly efficient adsorbents and offers a new approach to phosphopeptide analysis.

Impact of electronic cigarette usage on the onset of respiratory symptoms and COPD among Chinese adults.

The prevalence of dual usage and the relatively low cessation rate among e-cigarette (EC) users suggest that ECs have not demonstrated significant effectiveness as a smoking cessation tool. Furthermore, there has been a substantial increase in the prevalence of EC usage in recent years. Therefore, the objective of this study is to investigate the association between EC use and the incidence of respiratory symptoms and chronic obstructive pulmonary disease (COPD). A total of 10,326 participants aged between 20 and 55 years, without any respiratory diseases or COPD, were recruited for the study. These individuals attended employee physical examinations conducted at 16 public hospitals in Hebei province, China from 2015 to 2020. Logistic regression models were utilized to assess the association between EC use and the risk of respiratory symptoms and COPD using risk ratios along with their corresponding 95% confidence intervals. Restricted cubic spline functions were employed to investigate the dose-response non-linear relationship. The robustness of the logistic regression models was evaluated through subgroup analyses, and sensitivity analyses. During the 5-year follow-up period, a total of 1071 incident cases of respiratory symptoms and 146 incident cases of COPD were identified in this cohort study. After adjusting for relevant confounding factors, EC users demonstrated a respective increase in the risk of reporting respiratory symptoms and COPD by 28% and 8%. Furthermore, dual users who used both ECs and combustible cigarettes exhibited an elevated risk of incident respiratory symptoms and COPD by 41% and 18%, respectively, compared to those who had never used non-users of any cigarette products. The association between daily EC consumption and the development of respiratory symptoms, as well as COPD, demonstrated a significant J-shaped pattern. The potential adverse association between the consumption of ECs, particularly when used in combination with combustible cigarettes, and the development of respiratory symptoms and COPD necessitates careful consideration. Policymakers should approach ECs cautiously as a prospective smoking cessation tool.

Hydrogels Containing Chitosan-Modified Gold Nanoparticles Show Significant Efficacy in Healing Diabetic Wounds Infected with Antibiotic-Resistant Bacteria.

Purpose: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats. Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition. Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance. Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing.

Zirconium-rich magnetic polyoxometalate-based metal-organic framework: Tailored for phosphopeptide analysis from lung cancer A549 cells.

Polyoxometalate-based metal-organic frameworks (POMOFs) have become a promising affinity material for separation and enrichment. The analysis of protein phosphorylation represents a challenge for the development of efficient enrichment materials. Here, a novel zirconium-rich magnetic POMOF was successfully designed and prepared for the enrichment of phosphopeptides. The binding affinity of the nanomaterial partly came from Fe-O clusters in the MOF. The Lewis acid-base interactions between V-O clusters and zirconium ions in V10O28-Zr4+ and phosphate groups in phosphopeptides further strengthened the enrichment ability. The zirconium-rich magnetic POMOF was employed to capture phosphopeptides from non-fat milk, human saliva, and serum. Additionally, 748 unique phosphopeptide peaks were detected from the tryptic digests of lung cancer A549 cell proteins with a high specificity (86.9 %). POMOFs will become an active competitor for the design of protein affinity materials and will provide a new approach for phosphopeptide analysis.

Interferon regulatory factors inhibit TiLV replication by activating interferon-a3 in tilapia (Oreochromis niloticus).

Tilapia lake virus (TiLV) is an emerging virus that seriously threatens the tilapia industries worldwide. Interferon regulatory factors (IRFs), which are the crucial mediators regulating the response of interferon (IFN) to combat invading viruses, have not yet been reported in tilapia during TiLV infection. Here, six IRF (IRF1, IRF2, IRF4, IRF7, IRF8, and IRF9) homologs from tilapia were characterized and analyzed. These IRFs typically shared the conserved domains and phylogenetic relationship with IRF homologs of other species. Tissue distribution analysis showed that all six IRF genes were expressed in various tissues, with the highest expression in immune-related tissues. Furthermore, overexpression of IRFs in tilapia brain (TiB) cells significantly inhibited TiLV propagation, as evidenced by decreased viral segment 8 gene transcripts and copy numbers of viral segment 1. More importantly, all six IRF genes significantly enhanced the promoter activity of type I interferon-a3 (IFNa3) in TiB cells, suggesting that tilapia IRF genes serve as positive regulators in activating IFNa3. Surprisingly, the promoter activity of IFNa3 mediated by IRF genes was markedly inhibited post-TiLV infection, indicating that TiLV antagonized IRF-mediated IFN immune response. Taken together, six IRF genes of tilapia are highly conserved transcription factors that inhibit TiLV infection by activating the promoter of IFNa3, which is in turn restrained by TiLV. These findings broaden our knowledge about the functionality of IRF-mediated antiviral immunity in tilapia against TiLV infection and host-TiLV interaction, which lays a foundation for developing antiviral strategies in tilapia cultural industries.

A closed-loop process for spent washing solution from multi-metal contaminated soil: EDTA reclamation and recycling.

The proper disposal of spent soil washing solution is a great challenge to ethylenediamine tetraacetate (EDTA)-base soil washing technologies, particularly when the solution contains multi-metals. In this paper, we proposed an environmentally friendly disposal of multi-metal spent washing solution, in which the multi-metals were concentrated as hazardous precipitates for further safe disposal, and EDTA was reclaimed and recycled to further wash contaminated soil together with the cleansed process water. The results showed that Cr3+ was poorly removed by sole heavy-metal-capturing agent (HMCA) chelation because of the high solubility of HMCA-Cr, which also yielded a low percentage of EDTA reclamation in the multi-metal spent washing solution. We established a closed-loop process for the disposal of multi-metal spent washing solution by combining coagulation-flocculation-sedimentation and HMCA chelation. The novel recycling process was able to remove 99.67% Cu, 99.62% Pb, 92.48% Cd, 88.19% Sb, 84.38% As, and 82.39% Cr as precipitates from the real spent washing solution, and up to 95.64% of EDTA was reclaimed in the cleansed process water. On the average, the overall efficiency of the reclaimed EDTA solution could reach 65% of the fresh EDTA solution in extracting various HMs from contaminated soil. The recycling method provides an efficient and promising alternative for spent soil washing solution with both EDTA and process water reusage in a closed-loop process.

Therapeutic potential of hydrogen sulfide in osteoarthritis development.

The pathological mechanisms and treatments of osteoarthritis (OA) are critical topics in medical research. This paper reviews the regulatory mechanisms of hydrogen sulfide (H2S) in OA and the therapeutic potential of H2S donors. The review highlights the importance of changes in the endogenous H2S pathway in OA development and systematically elaborates on the role of H2S as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how H2S can lessen bone and joint inflammation by inhibiting leukocyte adhesion and migration, reducing pro-inflammatory mediators, and impeding the activation of key inflammatory pathways such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Additionally, H2S is shown to mitigate mitochondrial dysfunction and endoplasmic reticulum stress, and to modulate Nrf2, NF-κB, PI3K/Akt, and MAPK pathways, thereby decreasing oxidative stress-induced chondrocyte apoptosis. Moreover, H2S alleviates bone and joint pain through the activation of Kv7, K-ATP, and Nrf2/HO-1-NQO1 pathways. Recent developments have produced a variety of H2S donors, including sustained-release H2S donors, natural H2S donors, and synthetic H2S donors. Understanding the role of H2S in OA can lead to the discovery of new therapeutic targets, while innovative H2S donors offer promising new treatments for patients with OA.

Imaging evaluation of disc position and status after temporomandibular joint arthroscopic disc repositioning and suturing surgery.

Objective: This study aimed to explain the change of disc position at different over-corrected place after arthroscopic disc repositioning and suturing surgery. Study design: Patients treated with temporomandibular joint arthroscopic disc repositioning and suturing surgery were reviewed. All patients underwent magnetic resonance imaging (MRI) before, immediately after surgery and at 2-year follow-up. The position of disc was checked and the change was compared. Results: 133 patients were included in the final analysis with 203 TMJ sides. The incidence rate for anterior movement of the disc after surgery was 33.0 %. Disc repositioned between 12 and 1 o'clock showed smaller movement rate of 22.6 %, while higher movement rate of 53.6 % was seen when repositioned between 2 and 3 o'clock. Conclusions: After arthroscopic disc repositioning and suturing surgery for ADD patients, the repositioned disc showed tendency to move forward. 12 to 1 o'clock was optional disc site for repositioning while excessive over-correction was not recommended.

Husband smoking is associated with Wife's thyrotropin abnormality: A population-based cohort study among Chinese reproductive-aged women.

OBJECTIVES: To comprehensively assess the association of husband smoking with wives' thyrotropin abnormality. METHODS: This population-based retrospective cohort study included 2 406 090 Chinese reproductive-aged women who had participated twice in the National Free Pre-pregnancy Checkups Project between 2010 and 2020. Multivariate-adjusted odds ratios and 95% confidence intervals for subnormal and supranormal thyrotropin were estimated according to the husband's smoking status. RESULTS: Husband smoking at the first visit was associated with a 17% (15%-20%) and 26% (24%-28%) increased odds of subnormal thyrotropin and supranormal thyrotropin respectively compared to participants in neither-smoker group. In non-smoking participants with normal thyrotropin levels at the first visit, the corresponding increased risk of subnormal thyrotropin and supranormal thyrotropin at the second visit were 15% (12%-18%) and 19% (16%-21%) in contrast to participants without husband-smoking exposure. In non-smoking participants with abnormal thyrotropin levels at their first visit, husband smoking cessation was associated with 27% (17%-35%) and 36% (31%-40%) reduced odds of subnormal thyrotropin and supranormal thyrotropin at the second visit compared with the participants whose husband still smoking at the second visit. CONCLUSION: Husband smoking was associated with wives' subnormal thyrotropin and supranormal thyrotropin, and cessation of husband smoking could reduce the odds of thyrotropin abnormality. Couple-focused smoking intervention should be developed to reduce the burden of asymptomatic thyroid disease in females.

CTA-Based Radiomics and Area Change Rate Predict Infrarenal Abdominal Aortic Aneurysms Patients Events: A Multicenter Study.

RATIONALE AND OBJECTIVES: Clinical assessment of abdominal aortic aneurysm (AAA) intervention and rupture risk relies primarily on maximum diameter, but studies have shown that sole dependence on diameter has limitations. CTA-based radiomics, aneurysm and lumen area change rates (AACR, LACR) are measured to predict potential AAA events. MATERIALS AND METHODS: Between January 2017 and November 2022, 260 AAA patients from four centers who underwent two preoperative CTA examinations were included in this retrospective study. The endpoint event is defined as AAA rupture or repair. Patients were categorized into event and no-event groups based on the occurrence of endpoint event during follow-up. AACR and LACR were assessed using baseline and follow-up CTA, with radiomics features extracted from the baseline images. C-statistics and the Kaplan-Meier analysis were used to evaluate the predictive performance. RESULTS: A total of 193 eligible infrarenal AAA patients were included, 176 (91.2%) were man and 17 (8.8%) were woman. The median follow-up was 33.4 (14.2, 57.4) months. Seven models were constructed, comprising the aneurysm-based Radscore model, lumen-based Radscore model, intraluminal thrombus (ILT)-based Radscore model, AACR model, LACR model, clinical model (including high-density lipoprotein, D-dimer, and baseline aneurysm diameter), and a merged model. On the external validation set, the C-index of seven models were 0.713 (0.574-0.853), 0.642 (0.499-0.786), 0.727 (0.600-0.854), 0.619 (0.484-0.753), 0.680 (0.530-0.830), 0.690 (0.557-0.824) and 0.760 (0.651-0.869), in that order. In the Kaplan-Meier analysis, the merged model was best-divided patients into high/low-risk groups with Log-rank p < 0.0001. The AARC and LARC between non-event and event groups have significant differences (AACR: 1.4 cm2/y vs. 2.3 cm2/y, p < 0.0001; LACR: 0.3 cm2/y vs. 1.1 cm2/y, p < 0.0001). CONCLUSION: CTA-based radiomics, AACR and LACR have good predictive value for outcome event in infrarenal AAA patients.

An immune window of opportunity to prevent spontaneous abortion: prepregnancy peripheral leukocytes and subsets were associated with a decreased risk of spontaneous abortion.

STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Functional hemostatic hydrogels: design based on procoagulant principles.

Uncontrolled hemorrhage results in various complications and is currently the leading cause of death in the general population. Traditional hemostatic methods have drawbacks that may lead to ineffective hemostasis and even the risk of secondary injury. Therefore, there is an urgent need for more effective hemostatic techniques. Polymeric hemostatic materials, particularly hydrogels, are ideal due to their biocompatibility, flexibility, absorption, and versatility. Functional hemostatic hydrogels can enhance hemostasis by creating physical circumstances conducive to hemostasis or by directly interfering with the physiological processes of hemostasis. The procoagulant principles include increasing the concentration of localized hemostatic substances or establishing a physical barrier at the physical level and intervention in blood cells or the coagulation cascade at the physiological level. Moreover, synergistic hemostasis can combine these functions. However, some hydrogels are ineffective in promoting hemostasis or have a limited application scope. These defects have impeded the advancement of hemostatic hydrogels. To provide inspiration and resources for new designs, this review provides an overview of the procoagulant principles of hemostatic hydrogels. We also discuss the challenges in developing effective hemostatic hydrogels and provide viewpoints.

A Novel Method for Precision Measurement and Result Optimization of Detuning Angle for KDP Crystals.

In this paper, we investigate the theory of energy distribution when divergent light undergoes harmonic conversion in KDP crystals, and based on this theory, we design and construct a precision measuring instrument for the detuning angle of (KDP) Crystals (MIDC). The device can obtain the detuning angle of the crystal by a single measurement with an average measurement error of 72.78 urad. At the same time, it also has the function of scanning the full aperture of the crystals. Using the MIDC, it is possible to quickly measure the KDP crystal at a single point and quickly scan the crystal detuning angle at full aperture. In addition, we conduct a theoretical study on the variation of detuning angle caused by gravity-influencing factors under online conditions, propose an optimization formula for the offline measurement results of detuning angle, and calculate the optimized values of detuning angle for two kinds of crystals under 45° online conditions. We finally study the error source of the MIDC device, analyze the trend of the influence of positioning errors of the crystal and optical elements on the detuning angle measurement results, and provide theoretical support for the error monitoring and correction of MIDC.