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The low output current density of piezoelectric nanogenerators (PENGs) severely restricts their application for ambient mechanical energy harvest. This has been a key challenge in the development of PENG. Here, to conquer this, based on a piezoelectric material with high piezoelectric coefficient (Sm-PMN-PT), a new design of PENG with a three-dimensional intercalation electrode (IENG) is proposed. By creating many boundary interfaces inside the piezoelectric material, the total amount of surface polarization charges increased, which contributes to an increased current density. The IENG can output a maximum peak short-circuit current of 320 μA, and the corresponding current density 290 μA cm −2 is 1.93 and 1.61 times the record values of PENG and triboelectric nanogenerator (TENG), respectively. It can also charge a 1 μF capacitor from 0 V to 8 V in 21 cycles, and the equivalent surface charge density 1690 μC m −2 is 1.35 times the record value of TENG. Increasing the output current density is the key challenge for nanogenerators. Here, a new piezoelectric nanogenerator with a three-dimensional intercalation electrode is developed to reach 290 μA cm −2 by creating and utilizing many boundary interfaces.

Egg recognition is one of the most common strategies utilized by host birds to combat brood parasitism. Eggshell surface features (e.g., eggshell color and spots) are important cues for host egg recognition, enabling avian hosts to recognize and reject foreign eggs. The barn swallow (Hirundo rustica), as one host of the common cuckoo (Cuculus canorus), has demonstrated variation in their egg rejection propensity geographically. However, it remains unclear whether eggshell spots play an important role in their egg recognition. To this end, this study examined the role of eggshell spots in egg recognition in two populations of barn swallows. Our results revealed that in both Danzhou and Dongfang populations, the rejection rate of barn swallows for spotted eggs was significantly lower than that for eggs without spots, suggesting that eggshell spot signaling plays a pivotal role during the process of egg recognition in barn swallows. Our findings also indicated that egg shape (ovoid vs. round) did not affect egg recognition by barn swallows. This was most likely because the round shape did not deviate significantly from egg‐shaped properties, causing the inability of barn swallows to distinguish the difference in shape. We experimentally tested if egg spots were used as recognition cues in barn swallows (Hirundo rustica). The rejection rate of barn swallows for spotted eggs was significantly lower than that for spotless eggs, suggesting that eggshell spot signaling plays a pivotal role during the process of egg recognition in barn swallows.

Background Smartphone addiction has emerged as a widespread public health concern, especially among college students. This study examines the association between smartphone addiction and creativity among Chinese college students, as well as the underlying psychological mechanisms involved. A serial mediation model framework was conducted to explore the effect of smartphone addiction on creativity, taking into consideration the mediating roles of depression and executive function. Methods In this study, a sample of 691 Chinese college students was surveyed using the Mobile Phone Addiction Index, the Centre for Epidemiologic Studies - Depression Scale, the Behavior Rating Inventory of Executive Function - Adult Version, and the University Students’ Creativity Scale to examine the impact mechanism of smartphone addiction on creativity. Correlation and mediation model analyses were performed respectively using SPSS 22.0 and PROCESS 3.1. Results Correlation analysis showed that smartphone addiction was positively correlated with depression ( r = 0.298, P < 0.001) and executive function impairment ( r = 0.677, P < 0.001), while it was negatively associated with creativity ( r = -0.209, P < 0.001). Additionally, depression was positively correlated with executive function impairment ( r = 0.376, P < 0.001). Furthermore, creativity was negatively associated with depression ( r =-0.143, P < 0.001) and executive function impairment ( r = -0.291, P < 0.001). The mediation analysis indicated that smartphone addiction directly negatively predicted creativity, and also indirectly predicted creativity through the serial mediating role of depression and executive function impairment. Conclusion Smartphone addiction not only directly affected creativity, but also indirectly influenced it through both the independent mediating role of executive function, as well as their serial mediation pathway.

Background. The role of ketamine as an adjuvant for morphine in the treatment of cancer pain and immune functions has been confirmed. This study aimed to explore the role of morphine and ketamine on cancer pain and T cells of patients with cervical cancer (CC). Methods. T cells were isolated from peripheral blood mononuclear cells (PBMC) of CC patients by positive selection using anti-CD3 beads. The isolated T cells were assigned into three groups: the control group, the morphine group, and the morphine + ketamine (Mor + Ket) group. The percentages of CD4+ and CD8+ were analyzed by flow cytometry. The levels of interferon (IFN)-γ, interleukin (IL)-2, and IL-17 and the corresponding mRNA expression in vitro were determined using ELISA and qRT-PCR, respectively. Western blotting was used for detection of JAK3/STAT5 pathway-related proteins after naltrexone treatment in vitro. Afterwards, all the patients were further divided into the morphine group and the Mor + Ket group in accordance with the principles of the randomized and double-blind method to assess pain intensity. Results. Our in vivo results showed that drug combinations relieved cancer pain more effectively than morphine intervention. The in vitro results demonstrated that the combination of morphine and ketamine may decrease CD4+ percentage, CD4+/CD8+ ratio, and the levels of IFN-γ, IL-2, and IL-17 via the JAK3/STAT5 pathway. Conclusions. Our finding indicated that morphine-ketamine combination could improve cancer pain and repress immune function via the JAK3/STAT5 pathway in the progression of CC.

ObjectiveThis study aimed to introduce a novel laparoscopic haemostasis for myomectomy and investigate the independent risk factors for uterine fibroid recurrence.DesignA retrospective cohort study.SettingFollowing strengthening the reporting of observational studies in epidemiology (STROBE) criteria, a retrospective study of prospectively collected available data of the consecutive patients who underwent the myomectomy in the department of obstetrics and gynaecology of the single centre between February 2018 and December 2020.Participants177 patients who underwent laparoscopic myomectomy resection were enrolled in the present cohort study.Materials and methodsPatients were classified into two groups according to their different methods of haemostasis in laparoscopic surgery. Recurrence-free survival was compared between the groups during an average follow-up of nearly 2 years.ResultsOf the 177 patients from 672 consecutive patients in the retrospective cohort, laparoscopic circular suture and baseball suture were carried out in 102 (57.6%) and 75 (42.4%) patients, respectively. The total amount of blood lost during surgery varied significantly (37.6 vs 99.5 mL) (p<0.001). Univariable analyses identified that age ≥40 years, position at intramural myoma, multiple fibroids and largest fibroid volume ≥50 mm3 (HR 2.222, 95% CI 1.376 to 3.977, p=0.039; HR 3.625, 95% CI 1.526 to 6.985, p=0.003; HR 3.139, 95% CI 1.651 to 5.968, p<0.001; HR 2.328, 95% CI 0.869 to 3.244, p=0.040, respectively) are independent risk factor of the recurrence of uterine fibroids. The formula of the nomogram prediction model was established as the practical clinical tool.ConclusionThe laparoscopic continuous seromuscular circumsuture for myomectomy can effectively reduce the amount of surgical bleeding and accelerate the perioperative recovery for surgical safety. The main factors affecting the recurrence of uterine fibroids were age, location, number and volume of uterine fibroids. The nomogram can more straightforwardly assist clinicians to determine the risk of recurrence after laparoscopic myomectomy.

Upadacitinib, one of the Janus kinase (JAK) inhibitors, has gained global approval for treating various inflammatory and autoimmune diseases. However, despite the FDA's black box warning on all JAK inhibitors, further research is necessary to verify the potential risks associated specifically with upadacitinib. Therefore, this study conducted a comprehensive systematic review and meta-analysis to assess the safety profile of upadacitinib and explore potential dose-related differences. Relevant English publications were identified through a comprehensive search of eligible databases conducted in March 2024 and subsequently updated in May 2025. The inclusion criteria focused on randomized controlled trials that included safety data on upadacitinib. A total of 9,547 patients were involved in this meta-analysis. Upadacitinib treatment was associated with an increased risk of hepatic disorder, neutropenia, acne, herpes zoster, and increased creatine phosphokinase levels. Notably, the risks of hepatic disorder, neutropenia, and acne also exhibited a dose-dependent relationship. However, there was no significant association between upadacitinib treatment and an elevated risk of renal dysfunction, non-melanoma skin cancer (NMSC), major adverse cardiovascular event (MACE), or venous thromboembolic event (VTE). This study reveals that upadacitinib generally has a favorable safety profile, with increased risks of hepatic disorder, neutropenia, acne, especially at higher doses. There was no significant association with renal dysfunction, NMSC, MACE, or VTE. These findings may serve as an evidence base for potential future modifications or removal of the FDA's black box warning for upadacitinib.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified. Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14–90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78–6.02] vs. ROR 4.19 [95% CI, 3.56–4.91], p = 0.0147). Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80–21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95–248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65–5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8–72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78–6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, characterized by high invasion and metastasis. Aldo-keto reductase family 1 member C1 (AKR1C1) plays an important role in cancer cell proliferation and metastasis, and has gained attention as an anticancer drug target. Here, we report that the natural sesquiterpene lactone alantolactone (ALA) was shown to bind directly to AKR1C1 through the Proteome Integral Solubility Alteration (PISA) analysis, a label-free target identification approach based on thermal proteome profiling. Acting as a specific inhibitor of AKR1C1, ALA selectively inhibits the activity of AKR1C1 and ALA treatment in human non-small-cell lung cancer (NSCLC) cell results in a reduction in cell proliferation and metastasis, inhibition of AKR1C1 expression, and deactivation of STAT3. Moreover, ALA inhibited tumor growth in vivo , and the inhibition of AKR1C1 and STAT3 activation were also found in the murine xenograft model. Collectively, our work not only gives mechanistic insights to explain the bioactivity of ALA in anticancer but also provides opportunities of developing novel sesquiterpene lactone-based AKR1C1 inhibitors for the treatment of NSCLC.

Personal electronic devices have a general development trend of miniaturization, functionality, and wearability. Their wireless, sustainable, and independent operation is critically important, which requests new power technologies that can harvest the ambient environmental energy. Here, we report a new kind of 2D woven wearable triboelectric nanogenerator (2DW-WTNG) composed of core-shell fibers via the twisting process and weaving process in the textile manufacture. The 2DW-WTNG can convert the body motion energy into electricity with an output current of 575 nA and an output voltage of 6.35 V. At an external load of 50 MΩ, it generated a maximum power density of 2.33 mW/m 2 . Electricity can be produced from the 2DW-WTNG driven in arbitrary in-plane directions. A tiny displacement of 0.4 mm can drive the 2DW-WTNG, which verified its capability to harvest energy from small human movement. The robust 2DW-WTNG can work continuously for 12 h without obvious performance degradation.