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Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration‐resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron‐dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate‐specific membrane antigen (PSMA)‐targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane‐coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M‐gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA‐specific, CRPC‐targeting platform for ferroptosis induction with increased efficacy and safety. [ABSTRACT FROM AUTHOR]

Open biomass burning plays an important role in the formation of heavy pollution events during harvest seasons in China by releasing gases and particulate matters into the atmosphere. A better understanding of open biomass burning in China is required to assess its impacts on the air quality and especially on heavy haze pollution.By using datasets of MODIS fire spot, land cover, vegetation cover, biomass loading and emission factors, a biomass emission model is developed, which is then embedded to an air quality model (WRF-CUACE) to quantitatively assess impacts of biomass burning on surface PM2.5 concentration in China through sensitivity tests. Three simulation scenarios are designed to ensure that simulation results of revised scenarios are closer to actual atmospheric conditions according to the model evaluation. Results show that in October 2014, Northeast, South and Southwest China are regions of the largest contribution to biomass burning with the average monthly increased concentration of PM2.5 up to 30-60 μg·m-3, and even more than 100 μg·m-3 at local regions. In North, East and South China, biomass burning generally provides a contribution of PM2.5 concentration of 5-20 μg·m-3. In terms of the percentage of relative contribution, the value in Northeast China exceeds 50% in most regions. In South China, the relative contribution of biomass burning reaches 20%-50%, and even exceeds 60% in parts of Southwest China. While in North, Central and East China, the relative contribution of biomass burning is generally 10%-20%. In addition, the contribution of secondary aerosols in PM2.5 from biomass burning is also estimated. A group of sensitivity experiments are set up, with and without the gas emission from biomass burning. In Northeast China, the contribution concentration of secondary aerosols is only 0-10 μg·m-3, significantly lower than that in North, Central, East and South China, where the contribution concentration of secondary aerosols could reach 5-15 μg·m-3. In terms of the percentage of contribution to secondary aerosols in PM2.5 from biomass burning, the value in Northeast China is the lowest, which is less than 30% in most regions. And in South and Southwest China, the contribution percentage is relatively larger, which can reach 30%-50%. While in North, Central, East China and vast remote areas, the contribution percentage almost exceed 70%. Based on the above analysis, it is found that the percentage of secondary aerosols in PM2.5 from biomass burning drops when the biomass burning grows.

Summary: Clearance and adaptation to reactive oxygen species (ROS) are crucial for cell survival. As in other eukaryotes, the Neurospora catalases are the main enzymes responsible for ROS clearance and their expression are tightly regulated by the growth and environmental conditions. The RNA polymerase II carboxyl terminal domain (RNAPII CTD) kinase complex (CTK complex) is known as a positive elongation factor for many inducible genes by releasing paused RNAPII near the transcription start site and promoting transcription elongation. However, here we show that deletion of CTK complex components in Neurospora led to high CAT‐3 expression level and resistance to H2O2‐induced ROS stress. The catalytic activity of CTK‐1 is required for such a response. On the other hand, CTK‐1 overexpression led to decreased expression of CAT‐3. ChIP assays shows that CTK‐1 phosphorylates the RNAPII CTD at Ser2 residues in the cat‐3 ORF region during transcription elongation and deletion of CTK‐1 led to dramatic decreases of SET‐2 recruitment and H3K36me3 modification. As a result, histones at the cat‐3 locus become hyperacetylated to promote its transcription. Together, these results demonstrate that the CTK complex is negative regulator of cat‐3 expression by affecting its chromatin structure. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anesthetic effect of epidural pre-catheterization with low-concentration chloroprocaine during the second parturition. Methods: 180 second-trimester primiparas undergoing epidural analgesia in Maanshan Maternal and Child Health Care Hospital, Ma'anshan, China were randomly divided into 3 groups, viz, pre-catheterization with chloroprocaine (group A), routine chloroprocaine (group B), and routine ropivacaine (group C), with 60 patients per group. The time of onset of analgesia, visual analogue scale (VAS) scores, modified Bromage score (MBS) scores, neonatal 1- and 5-min Apgar scores, oxytocin use, number of cesarean sections, volume of postpartum hemorrhage, and incidence of anesthesia-related complications were compared among the three groups. Results: Onset time of anesthesia was significantly shorter in women in groups A and B than in group C (p < 0.05). The VAS scores at 5 and 15 min after analgesia were lower in groups A and B than in group C (p < 0.05). There were no significant differences in VAS scores among the three groups from 30 min after analgesia to the end of the first stage of labor (p > 0.05). There were also no significant differences in MBS scores, neonatal Apgar scores, oxytocin use, number of cesarean sections, volume of postpartum hemorrhage, and incidence of adverse reactions among the three groups (p > 0.05). Conclusion: Individualized mode of analgesia involving the administration of low-concentration chloroprocaine to primiparas using an epidural catheter has timely onset of analgesia, good efficacy, high safety, rapid metabolism, and minimal adverse reactions. Further studies involving multiple centers and long-term follow-up are necessary. [ABSTRACT FROM AUTHOR]

Background: Postpartum urinary retention is a common complication following caesarean section, with significant implications for patient comfort and recovery. Combined spinal and epidural anaesthesia is frequently employed for caesarean section, but postpartum urinary retention remains a clinical concern despite its benefits. This study aimed to investigate the effectiveness of hydromorphone hydrochloride combined with bupivacaine for combined spinal and epidural anaesthesia in reducing postpartum urinary retention., Methods: A retrospective analysis was conducted on patients who received combined spinal and epidural anaesthesia for caesarean section. The control group received bupivacaine, whereas the hydromorphone hydrochloride combined with bupivacaine spinal-epidural anaesthesia (HB) group received hydromorphone hydrochloride combined with bupivacaine. Data on demographics, anaesthesia, operative characteristics, postoperative urinary retention and adverse events were collected and analysed., Results: The study enrolled 105 patients, with a control group (n = 51) receiving bupivacaine spinal-epidural anaesthesia and an observation group (n = 54) receiving hydromorphone hydrochloride combined with bupivacaine spinal-epidural anaesthesia. The incidence of postoperative urinary retention was significantly lower in the HB group than in the control group (3.70% vs. 17.65%, p = 0.044). Furthermore, the HB group exhibited a shorter time to first voiding after anaesthesia (5.72 ± 1.26 h vs. 6.28 ± 1.35 h, p = 0.029), lower peak postvoid residual volume (168.57 ± 25.09 mL vs. 180.43 ± 30.21 mL, p = 0.032), decreased need for postoperative catheterisation (5.56% vs. 21.57%, p = 0.034) and shorter duration of urinary catheterisation (10.92 ± 2.61 h vs. 12.04 ± 2.87 h, p = 0.039) than the control group. Correlation analysis supported a negative correlation between hydromorphone supplementation and parameters related to postoperative urinary retention. Multivariate regression analysis demonstrated a significant association between the duration of urinary catheterisation and the use of hydromorphone with the occurrence of postoperative urinary retention, providing further insights into the multifactorial nature of this postoperative complication., Conclusions: The addition of hydromorphone hydrochloride to bupivacaine for combined spinal and epidural anaesthesia was associated with a reduced incidence of postpartum urinary retention and improved postoperative voiding parameters, without significantly increasing the risk of adverse events., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Objective To investigate the therapeutic effect of targeting and killing CD248-positive myofibroblasts on bleomycin-induced pulmonary fibrosis in mice. Methods IgG78-DM1, an antibody-maytansine 1 (DM1) conjugate targeting CD248, was prepared. The drug conjugation efficiency was measured and calculated by UV spectrophotometer, and the identification of IgG78-DM1 was performed through SDS-PAGE and Western blot analysis. In vitro, the binding activity of IgG78-DM1 on CD248-positive myofibroblasts was detected by flow cytometry and the cytotoxicity of IgG78-DM1 to CD248-positive myofibroblasts was evaluated by CCK-8 assay. In vivo, C57BL/6 male mice were randomly divided into control group, idiopathic pulmonary fibrosis group, human IgG-DM1 (hIgG-DM1) control group, and IgG78-DM1 treatment group. Then, the mouse models with pulmonary fibrosis induced by bleomycin were constructed. Two weeks later, the animal models were intravenously injected with IgG78-DM1. After the treatment of two weeks, lung tissues were collected for Masson staining and Sirius Red staining to evaluate the degree of pulmonary fibrosis. Real-time fluorescence quantitative PCR was used to measure the expression levels of CD248, as well as markers of fibroblastic activation including alpha-smooth muscle actin (α-SMA) and type I collagen alpha 1 (COL1A1). The safety of IgG78-DM1 was preliminarily assessed by conducting liver and kidney function tests. Results IgG78-DM1 was successfully prepared, and its drug conjugation ratio was 3.2. The antibody structure remained stable after conjugation, allowing effective binding and cytotoxicity against CD248-positive myofibroblasts. After treatment with IgG78-DM1, the degree of pulmonary fibrosis in mice significantly reduced, accompanied by the decrease of the expression of CD248, α-SMA, and COL1A1. The liver and kidney function of the mice remained at normal levels compared to the normal control group. Conclusion IgG78-DM1 effectively inhibits pulmonary fibrosis in mice by targeting and killing CD248-positive myofibroblasts. The safety of this strategy is preliminarily assessed.