A Rab39-Klp98A-Rab35 endocytic recycling pathway is essential for rapid Golgi-dependent furrow ingression.

Ingression of the plasma membrane is an essential part of the cell topology-distorting repertoire and a key element in animal cell cytokinesis. Many embryos have rapid cleavage stages in which they are furrowing powerhouses, quickly forming and disassembling cleavage furrows on timescales of just minutes. Previous work has shown that cytoskeletal proteins and membrane trafficking coordinate to drive furrow ingression, but where these membrane stores are derived from and how they are directed to furrowing processes has been less clear. Here, we identify an extensive Rab35/Rab4>Rab39/Klp98A>trans-Golgi network (TGN) endocytic recycling pathway necessary for fast furrow ingression in the Drosophila embryo. Rab39 is present in vesiculotubular compartments at the TGN where it receives endocytically derived cargo through a Rab35/Rab4-dependent pathway. A Kinesin-3 family member, Klp98A, drives the movements and tubulation activities of Rab39, and disruption of this Rab39-Klp98A-Rab35 pathway causes deep furrow ingression defects and genomic instability. These data suggest that an endocytic recycling pathway rapidly remobilizes membrane cargo from the cell surface and directs it to the trans-Golgi network to permit the initiation of new cycles of cleavage furrow formation.

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

Surface Epitaxial Growth of 2D/2D Bi2O2S/CdS Heterojunction Photoanodes and Their Photoelectrochemical Properties.

Constructing high catalytic activity heterojunctions to compensate for the shortcomings of single catalysts has promoted the development of semiconductor catalysts in photoelectrochemical (PEC) water splitting. In this case, the 2D/2D Bi2O2S/CdS composite was successfully constructed by an in situ surface epitaxial growth method. At 1.23 V vs RHE, the catalytic activity of Bi2O2S/CdS with a 2D/2D heterojunction is the highest, and the current density of the Bi2O2S/CdS photoanode is 3.46 mA/cm2. Compared with the Bi2O2S photoanode (0.59 mA/cm2), the performance has been improved by 5.86 times. In electrochemical impedance spectroscopy testing, the arc radius of 2D/2D Bi2O2S/CdS is smaller than that of Bi2O2S, indicating faster charge-transfer kinetics. The data show that the 2D/2D heterojunction with surface-surface contact successfully enhances the catalytic activity of Bi2O2S, greatly elevating the efficiency of charge separation and migration. This study provides a method to enhance the PEC activity in type-I heterojunction photoelectrodes, promoting the application of Bi2O2S-based materials in photoelectrochemistry.

Alkylaluminum Complexes Featuring Bridged Bis-Formylfluorenimide Ligands for Hydroboration of Aldehyde, Ketone, and Imines.

Three bis-formylfluorenimide ligands with different bridging groups were designed and synthesized, leading to the successful preparation of six novel alkylaluminum complexes through their reaction with alkylaluminum reagents (AlMe3 or AlEt3). Complexes 1 and 2 were obtained by the reaction of 1,2-propylene-bridged diamine (L1) with AlMe3 or AlEt3. By reacting 1,2-cyclohexylene-bridged diamine (L2) with AlMe3 or AlEt3 to obtain complexes 3 and 4. The above ligands formed a bidentate four-coordinate structure with alkylaluminum, which involved the elimination of one alkyl group as the ligand reacted with alkylaluminum. The complexes 5 and 6 were synthesized through the reaction of 1,2-phenylene-bridged diamine (L3) with AlEt3 in toluene or tetrahydrofuran. Notably, L3 exhibited unique reactivity compared with the other ligands, which formed a tridentate four-coordinated structure when reacting with alkylaluminum. The formation of the tridentate complex resulted from the introduction of a benzimidazole derivative or tetrahydrofuran (THF) molecule along with the elimination of two alkyl groups during its coordination with alkylaluminum. All complexes were characterized via 1H NMR, 13C NMR, and elemental analysis, with structural determination confirmed through X-ray. Furthermore, the catalytic activity in the hydroboration reaction of aldehyde, ketone, and imines was investigated with these complexes as catalysts. Among them, complex 1 demonstrated excellent catalytic performance (up to 99% yield) and broad substrate compatibility (more than 30 substrates) at low catalyst loading (1 mol %) under mild reaction conditions.

Combination of eriocalyxin B and homoharringtonine exerts synergistic anti-tumor effects against t(8;21) AML.

Understanding the molecular pathogenesis of acute myeloid leukemia (AML) with well-defined genomic abnormalities has facilitated the development of targeted therapeutics. Patients with t(8;21) AML frequently harbor a fusion gene RUNX1-RUNX1T1 and KIT mutations as "secondary hit", making the disease one of the ideal models for exploring targeted treatment options in AML. In this study we investigated the combination therapy of agents targeting RUNX1-RUNX1T1 and KIT in the treatment of t(8;21) AML with KIT mutations. We showed that the combination of eriocalyxin B (EriB) and homoharringtonine (HHT) exerted synergistic therapeutic effects by dual inhibition of RUNX1-RUNX1T1 and KIT proteins in Kasumi-1 and SKNO-1 cells in vitro. In Kasumi-1 cells, the combination of EriB and HHT could perturb the RUNX1-RUNX1T1-responsible transcriptional network by destabilizing RUNX1-RUNX1T1 transcription factor complex (AETFC), forcing RUNX1-RUNX1T1 leaving from the chromatin, triggering cell cycle arrest and apoptosis. Meanwhile, EriB combined with HHT activated JNK signaling, resulting in the eventual degradation of RUNX1-RUNX1T1 by caspase-3. In addition, HHT and EriB inhibited NF-κB pathway through blocking p65 nuclear translocation in two different manners, to synergistically interfere with the transcription of KIT. In mice co-expressing RUNX1-RUNX1T1 and KITN822K, co-administration of EriB and HHT significantly prolonged survival of the mice by targeting CD34+CD38- leukemic cells. The synergistic effects of the two drugs were also observed in bone marrow mononuclear cells (BMMCs) of t(8;21) AML patients. Collectively, this study reveals the synergistic mechanism of the combination regimen of EriB and HHT in t(8;21) AML, providing new insight into optimizing targeted treatment of AML.

Abnormalities of retinal function in type 2 diabetes mellitus patients without clinical diabetic retinopathy detected by multifocal electroretinogram.

OBJECTIVE: To study the changes of retinal function in type 2 diabetes mellitus(DM) patients without apparently diabetic retinopathy via multifocal electroretinogram. METHODS: Thirty-six type 2 DM patients (72 eyes) without visible diabetic retinopathy were selected as the experimental group, and thirty-five healthy subjects (70 eyes) were selected as the control group. All subjects were underwent multifocal electroretinogram (mf- ERG). RESULTS: Compared with the control group, the implicit time delay of the P1 wave in the first ring, third ring, fourth ring, and fifth ring of the experimental group was significant (t = -3.154, p = 0.004, t = -8.21, p = 0.000, t = -3.067, p = 0.004, t = -4.443, p = 0.000, respectively). The implicit time of the N1 wave in the fourth- and fifth-ring were also significantly delayed compared with the control group (t = -3.549, p = 0.001, t = 2.961, p = 0.005, respectively). Compared with the control group, the implicit time of the P1 wave and N1 wave in the temporal region of the experimental group were delayed (t = -2.148, p = 0.037, t = -2.834, p = 0.007, respectively). There were no significant difference between the experimental group and the control group of the temporal area in the amplitude density of P1 wave, N1 wave. There was no difference in the implicit time and amplitude density of the N1 and P1 waves in the nasal region between the experimental group and the control group. The multifocal electroretinogram complex parameters showed better specificity and sensitivity in the diagnosis of diabetic retinopathy. CONCLUSION: The multifocal electroretinogram can detect abnormal changes in the retina of type 2 DM patients without visible diabetic retinopathy. The multifocal electroretinogram complex parameter is a potential indicator for the early diagnosis of diabetic retinopathy.

Convolutional neural network models applied to neuronal responses in macaque V1 reveal limited nonlinear processing.

Computational models of the primary visual cortex (V1) have suggested that V1 neurons behave like Gabor filters followed by simple nonlinearities. However, recent work employing convolutional neural network (CNN) models has suggested that V1 relies on far more nonlinear computations than previously thought. Specifically, unit responses in an intermediate layer of VGG-19 were found to best predict macaque V1 responses to thousands of natural and synthetic images. Here, we evaluated the hypothesis that the poor performance of lower layer units in VGG-19 might be attributable to their small receptive field size rather than to their lack of complexity per se. We compared VGG-19 with AlexNet, which has much larger receptive fields in its lower layers. Whereas the best-performing layer of VGG-19 occurred after seven nonlinear steps, the first convolutional layer of AlexNet best predicted V1 responses. Although the predictive accuracy of VGG-19 was somewhat better than that of standard AlexNet, we found that a modified version of AlexNet could match the performance of VGG-19 after only a few nonlinear computations. Control analyses revealed that decreasing the size of the input images caused the best-performing layer of VGG-19 to shift to a lower layer, consistent with the hypothesis that the relationship between image size and receptive field size can strongly affect model performance. We conducted additional analyses using a Gabor pyramid model to test for nonlinear contributions of normalization and contrast saturation. Overall, our findings suggest that the feedforward responses of V1 neurons can be well explained by assuming only a few nonlinear processing stages.

Low-frequency pulsed electromagnetic fields alleviate the condylar cartilage degeneration and synovitis at the early stage of temporomandibular joint osteoarthritis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is characterized by articular cartilage degeneration and progressive synovitis. How to effectively inhibit TMJOA in the early stage has been a hot topic in the biomedical field. As a non-invasive physiotherapy, pulsed electromagnetic field (PEMF) treatment has shown great potential in the treatment of osteoarthritis (OA) in extremity joints. OBJECTIVE: This study aims to investigate the biological effect of PEMF intervention on TMJ cartilage degeneration and synovium inflammation at the early stage of TMJOA. METHODS: PEMF (2.0 mT, 15 Hz, 2 h/day) treatment was given to rats in which TMJOA was induced by applying the unilateral anterior crossbite (UAC). Histological and immunohistochemical staining, TUNEL assay, real-time PCR and western blotting assay were performed to detect the changes of the morphology and the expression of pro-inflammatory and degradative factors in condylar cartilage and synovium. RESULTS: Obvious condylar cartilage degeneration, characterized by decreased cartilage thickness, degraded cartilage extracellular matrix, increased expression of pro-inflammatory and degradative factors (TNF-α, IL-1ß, MMP-13, ADAMTS-5, IL-6, MMP-3, MMP-9 and COL-X) and increased chondrocytes death, was observed in UAC group, accompanied by synovium hyperplasia and up-regulation of pro-inflammatory and degradative factors in synovium. PEMF intervention reversed the decreased cartilage thickness at 3 weeks and degraded cartilage extracellular matrix at 6 weeks. Moreover, the up-regulation of pro-inflammatory, degradative and hypertrophyic factors and chondrocytes death in condylar cartilage induced by UAC were inhibited to some extent. In addition, the synovium hyperplasia and the up-regulation of pro-inflammatory and degradative factors in synovium were inhibited at 3 weeks and 6 weeks. CONCLUSIONS: Appropriate PEMF stimulation can reverse the loss of cartilage extracellular matrix, the chondrocytes death, the increased expression of pro-inflammatory and degradative factors in cartilage, the decreased cartilage thickness and synovium inflammation induced by UAC at the early stage of TMJOA to some extent. PEMF stimulation may be a promising method in clinical TMJOA treatment.

Relationship between pain resilience and pain catastrophizing in older patients after total knee arthroplasty: Chain-mediating effects of cognitive emotion regulation and pain management self-efficacy.

This study aimed to determine whether the relationship between pain resilience and pain catastrophizing in older patients after total knee arthroplasty (TKA) was mediated by cognitive emotion regulation strategies (CERS) and pain management self-efficacy (PMSE). Convenience cluster sampling was used in this cross-sectional study to recruit 382 older adults. The results revealed that pain catastrophizing was negatively correlated with pain resilience, adaptive CERS, and PMSE; however, it was positively correlated with maladaptive CERS (all p < 0.01). Mediation analysis revealed that both CERS (adaptive and maladaptive) and self-management independently and sequentially mediated the relationship between pain resilience and pain catastrophizing in older patients who underwent TKA. These findings demonstrate that CERS (adaptive and maladaptive) and PMSE play chain-mediating roles in the correlation between pain resilience and pain catastrophizing in older patients after TKA.

Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

BACKGROUND: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. METHODS: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. RESULTS: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89). CONCLUSIONS: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

The pulse of morphogenesis: actomyosin dynamics and regulation in epithelia.

Actomyosin networks are some of the most crucial force-generating components present in developing tissues. The contractile forces generated by these networks are harnessed during morphogenesis to drive various cell and tissue reshaping events. Recent studies of these processes have advanced rapidly, providing us with insights into how these networks are initiated, positioned and regulated, and how they act via individual contractile pulses and/or the formation of supracellular cables. Here, we review these studies and discuss the mechanisms that underlie the construction and turnover of such networks and structures. Furthermore, we provide an overview of how ratcheted processivity emerges from pulsed events, and how tissue-level mechanics are the coordinated output of many individual cellular behaviors.

NLRP3-GABA signaling pathway contributes to the pathogenesis of impulsive-like behaviors and cognitive deficits in aged mice.

BACKGROUND: Perioperative neurocognitive disorders (PND), such as delirium and cognitive impairment, are commonly encountered complications in aged patients. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is aberrantly synthesized from reactive astrocytes following inflammatory stimulation and is implicated in the pathophysiology of neurodegenerative diseases. Additionally, the activation of NOD-like receptor protein 3 (NLRP3) inflammasome is involved in PND. Herein, we aimed to investigate whether the NLRP3-GABA signaling pathway contributes to the pathogenesis of aging mice's PND. METHODS: 24-month-old C57BL/6 and astrocyte-specific NLRP3 knockout male mice were used to establish a PND model via tibial fracture surgery. The monoamine oxidase-B (MAOB) inhibitor selegiline (1 mg/kg) was intraperitoneally administered once a day for 7 days after the surgery. PND, including impulsive-like behaviors and cognitive impairment, was evaluated by open field test, elevated plus maze, and fear conditioning. Thereafter, pathological changes of neurodegeneration were explored by western blot and immunofluorescence assays. RESULTS: Selegiline administration significantly ameliorated TF-induced impulsive-like behaviors and reduced excessive GABA production in reactive hippocampal astrocytes. Moreover, astrocyte-specific NLRP3 knockout mice reversed TF-induced impulsive-like and cognitive impairment behaviors, decreased GABA levels in reactive astrocytes, ameliorated NLRP3-associated inflammatory responses during the early stage, and restored neuronal degeneration in the hippocampus. CONCLUSIONS: Our findings suggest that anesthesia and surgical procedures trigger neuroinflammation and cognitive deficits, which may be due to NLRP3-GABA activation in the hippocampus of aged mice.

Constructing Dual Cocatalysts of Ni2P-NiS-Decorated TiO2 for Boosting Photocatalytic H2 Evolution.

The loading of cocatalysts is an effective approach to optimize the separation of carriers during photocatalytic processes. Among them, cocatalysts often work independently during the photocatalytic production of H2. However, an investigation of the synergistic effect of dual cocatalysts is beneficial for further promoting photocatalytic H2 production activity. In this work, dual cocatalyst Ni2P-NiS-modified TiO2 nanosheets were fabricated through a solvent evaporation method. The investigation indicates that Ni2P-NiS can widen the light absorption range and reduce the contact angle between TiO2 and water from 26.71 to 8.27°, which facilitates the adsorption of water molecules. Besides, the introduction of Ni2P-NiS can decrease the overpotential of H2 evolution and induce more electrochemically active surface area. The photocatalytic tests show that the H2 production rate of 15% Ni2P-NiS/TiO2 can reach up to 4891.6 µmol·g-1·h-1, which is 30.2, 4.4, and 1.3 times than pure TiO2 (161.8 µmol·g-1·h-1), 15% Ni2P/TiO2 (1112.1 µmol·g-1·h-1), and 15% NiS/TiO2 (3678.1 µmol·g-1·h-1), respectively. The enhancement mechanism of photocatalytic H2 production is attributed to the Schottky barrier effect between Ni2P-NiS nanoparticles and TiO2 nanosheets, which can enormously promote the interface charge separation and transfer, and enhance the kinetics of H2 production. This work provides a potential strategy for enhancement H2 production using appropriate dual cocatalyst-decorated semiconductor materials.

Hole Storage Interfacial Regulation of Sb2Se3 Photocathode with Significantly Enhanced Photoelectrochemical Performance.

Although interfacial engineering materials for antimony selenide (Sb2Se3) photocathodes have been intensively studied, most of the previous research has focused on the development of photogenerated electron transfer promoters. In this work, Sb2Se3 photocathodes are innovatively modified by using ferrihydrite (Fh), which has been widely used as a hole storage layer in photoanodes. After modifying Fh, the photocurrent density of the Sb2Se3 photocathode was increased from -0.27 to -1.6 mA cm-2 at 0 VRHE with the onset potential positive shift about 150 mV, and an impressive injection efficiency of 83.84% was achieved. The major contribution of Fh to the photoelectrochemical (PEC) performance enhancement was demonstrated by various characterization studies. The results show that the enhancement performance of PEC is largely attributed to the capture of back-migrating holes by Fh, the reduction of interfacial charge transfer resistance, and the significant increase in electrochemical active surface area (ECSA). This work presents new insights into the application of hole storage layers in Sb2Se3-based photocathodes.

Clinical and Proteomic-Based Molecular Characterizations of Invasive and Noninvasive Somatotroph PitNETs.

INTRODUCTION: Somatotroph pituitary neuroendocrine tumours (PitNETs) are characterized by complex and variable biological behaviours with unpredictable patterns of growth and invasiveness. The molecular mechanisms and reliable predictors of biological markers of invasiveness remain unknown. METHODS: Seventy-two acromegaly patients were consecutively enrolled. Data-independent acquisition-based proteomics and ingenuity pathway analysis were conducted between invasive and noninvasive somatotroph PitNETs. The expression of selected biomarkers was verified in PitNET tissue, and its correlation with various clinical indicators and outcomes of these tumours was assessed. The invasive phenotypes of GH3 cells were validated in vitro. RESULTS: Patients with invasive somatotroph PitNETs were significantly younger at onset and diagnosis, with significantly higher secretion and faster growth and a lower long-term biochemical response rate than patients with noninvasive somatotroph PitNETs. Proteomic data were evaluated in a consecutively collected sample of 19 (10 invasive and 9 noninvasive somatotroph PitNETs) tumours and indicated a distinct proteomic pattern. The enriched and important pathways included IL-4, PDGF, PTEN, VEGF, PI3K/AKT, FAK, and other pathways that were significantly associated with tumour proliferation, migration, and invasion. High cathepsin Z (CTSZ) expression was found in invasive somatotroph PitNETs and significantly positively correlated with parameters of tumour invasion and growth. In Ctsz-overexpressing GH3 cells, cell proliferation, invasion, and migration were consequently increased. CONCLUSION: It is more difficult for patients with invasive somatotroph PitNETs to achieve remission than those with noninvasive somatotroph PitNETs, and proteomic data analysis has revealed the high expression of CTSZ as a contributing factor to invasive transformation and poor prognosis in somatotroph PitNETs for the first time.

Regioselective [2 + 1] photocycloaddition of 2-pyridones with diazo compounds.

Herein, we report a novel regioselective [2 + 1] cyclization reaction of 2-pyridones with carbenes generated in situ via visible light irradiation, without the requirement for catalysts or additives. The diverse functional groups of 2-pyridones and diazo compounds exhibit good tolerance, enabling the rapid synthesis of highly valuable cyclopropanated dihydro-2-pyridone scaffolds with exceptional regio- and stereoselectivity. Furthermore, DFT calculations provide a comprehensive explanation for the regio- and stereoselectivity observed in the reaction.

The Novel Fluorescent Probe Toward Yttrium(III) and its Bioimaging.

In this paper, the novel fluorescence probe XP based on Schiff-base was designed, synthesized and characterized, which could detect Y3+selectively and sensitively. The recognition mechanism of XP toward Y3+ was studied by Job's plot and HRMS. It was investigated that stoichiometric ratio of the probe XP conjugated with Y3+ was 1:2. And the detection limit was calculated as 0.30 µM. In addition, Y3+ was recognized by the test paper made from XP. And the probe XP could detect  Y3+ selectively in Caenorhabditis elegans and the main organs of mice. Thus, XP was considered to have some potential for application in bioimaging.

Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

PURPOSE: Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40 mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. METHODS: Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39 mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. RESULTS: Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1 week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36 months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. CONCLUSIONS: With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.