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Jacky WY Lee,1 Jimmy SM Lai,1 Doris WF Yick,2 Can YF Yuen21Department of Ophthalmology, University of Hong Kong, 2Department of Ophthalmology, The Caritas Medical Centre, Kowloon West Cluster, Hong Kong, People’s Republic of ChinaBackground: The purpose of this study was to compare the efficacy and safety of argon laser peripheral iridoplasty (ALPI) and systemic intraocular pressure (IOP)-lowering medications in the immediate management of acute phacomorphic angle closure.Methods: Consecutive cases of acute phacomorphic angle closure were randomized to receive ALPI and an intravenous or oral carbonic anhydrase inhibitor as initial treatment. Intravenous mannitol was administered for presenting IOP > 60 mmHg or IOP > 40 mmHg 2 hours posttreatment in both arms.Results: Of 10 consecutive cases, six received medical therapy and four received ALPI. Fifty percent in the medical group and none in the ALPI group required intravenous mannitol. The ALPI group took less time to achieve IOP < 25 mmHg (18.8 ± 7.5 minutes versus 115.0 ± 97.0 minutes, P = 0.001, F test); had a greater IOP reduction within 30 minutes (69.8% ± 7.7% versus 40.9 ± 23.9%, P = 0.03, t-test); and had a consistently smaller post-attack cup to disc ratio (0.50 ± 0.02 versus 0.60 ± 0.20, P = 0.002, F test).Conclusion: ALPI offers greater safety, consistency, and efficacy than systemic IOP-lowering medications as initial treatment for phacomorphic angle closure.Keywords: phacomorphic, glaucoma, argon laser peripheral iridoplasty, medical, intraocular pressure

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

A 63-year-old man presented with delayed inferior ST-elevation myocardial infarction complicated with ventricular septal rupture (VSR). He developed cardiogenic shock and respiratory failure requiring intubation and Impella (Abiomed) support.

Chronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis-associated CPP remain underdeveloped. Here, we examined the role of the voltage-gated sodium (Na V ) channel Na V 1.7 in (i) the sensitivity of vagina-innervating sensory afferents and investigated whether (ii) Na V 1.7 inhibition reduces nociceptive signals from the vagina and (iii) ameliorates endometriosis-associated CPP. The mechanical responsiveness of vagina-innervating sensory afferents was assessed with ex vivo single-unit recording preparations. Pain evoked by vaginal distension (VD) was quantified by the visceromotor response (VMR) in vivo. In control mice, pharmacological activation of Na V 1.7 with OD1 sensitised vagina-innervating pelvic afferents to mechanical stimuli. Using a syngeneic mouse model of endometriosis, we established that endometriosis sensitised vagina-innervating pelvic afferents to mechanical stimuli. The highly selective Na V 1.7 inhibitor Tsp1a revealed that this afferent hypersensitivity occurred in a Na V 1.7-dependent manner. Moreover, in vivo intra-vaginal treatment with Tsp1a reduced the exaggerated VMRs to VD which is characteristic of mice with endometriosis. Conversely, Tsp1a did not alter ex vivo afferent mechanosensitivity nor in vivo VMRs to VD in Sham control mice. Collectively, these findings suggest that Na V 1.7 plays a crucial role in endometriosis-induced vaginal hyperalgesia. Importantly, Na V 1.7 inhibition selectively alleviated endometriosis-associated CPP without the loss of normal sensation, suggesting that selective targeting of Na V 1.7 could improve the quality of life of women with endometriosis., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Waldenstrom macroglobulinaemia (WM), the predominant subtype of lymphoplasmacytic lymphoma with bone marrow involvement and serum IgM paraprotein, is a haematological condition commonly associated with renal parenchymal involvement. However, antineutrophil cytoplasmic antibody (ANCA)-negative pauci-immune crescentic glomerulonephritis (PICGN) in kidney infiltrated by lymphoma is very rare, with only two cases described in chronic lymphocytic leukaemia in English literature so far. We herein report the first patient with WM developing ANCA-negative PICGN. He was a 76-year-old male who presented with elevated serum globulin level and bilateral groin lymph node enlargement, subsequently diagnosed to have WM after pathologic examination of the bone marrow and groin lymph node. One month later, he was found to have acute kidney injury and proteinuria. Renal biopsy confirmed the presence of parenchymal involvement by WM accompanied by PICGN; while ANCA testing was negative. He was treated with pulse methylprednisolone followed by oral prednisolone. In addition, six courses of intravenous rituximab and oral cyclophosphamide were given. There was significant improvement in both his renal and haematological conditions. The clinical course of this case suggested that ANCA-negative PICGN may represent a paraneoplastic syndrome and a rare manifestation of WM-associated renal lesion. Early kidney biopsy and prompt treatment may improve the outcome of patients., (© 2024 Asian Pacific Society of Nephrology.)

The activation of various homopropargylic pyridines by cis-[RuII/OsII(dppm)2Cl2] (dppm = 1,1-bis(diphenylphosphino)methane) has previously been shown to generate a diverse array of metallacycles and metalated heterocyclic complexes. However, a minor structural modification of introducing a halide onto the pyridyl group of the alkyne substrate resulted in the formation of unprecedented Ru(II)/Os(II)-haloquinolizine complexes. These complexes display (1) κ2(X,C)-haloquinolizine chelates arising from the cycloisomerization of HC≡CC(OH)(CH2(6-X-2-py))(Ph) on [RuII/OsII(dppm)2]2+ moieties via a vinylidene pathway, (2) five-membered Ru/Os-X-C-N-C rings (X = F, Cl, Br) ortho- and peri-fused to quinolizinium skeletons, and (3) uncommon M-X-R bonding interactions that are atypical in coordination complexes. Despite being divalent and integrated into a five-membered Ru-X-C-N-C ring system, the X atoms in the Ru(II) complexes are susceptible to substitution by O in the presence of -OH, resulting in the formation of quinolizinium-fused ruthenaoxazole complexes. Overall, this work highlights the importance of considering metal-halocarbon bonding interactions in catalytic or coordination designs., (© 2024 Wiley‐VCH GmbH.)

Introduction: The farnesoid X receptor (FXR) is a crucial regulator in the intestine, maintaining bile acid homeostasis. Inhibiting intestinal FXR shows promise in managing inflammatory bowel and liver diseases by reducing bile acid accumulation. Additionally, changes in FXR expression could serve as a potential biomarker for intestinal diseases. Therefore, developing an imaging probe for FXR holds significant potential for the early detection, simultaneous treatment, and monitoring of FXR-related diseases., Objectives: The study aimed to develop a bioimaging probe for FXR by conjugating obeticholic acid (OCA), an FXR agonist, to an iridium(III) complex, and to investigate its application for targeting FXR in intestinal cells., Methods: OCA was conjugated to an iridium(III) complex to generate the novel complex 1. The effect of complex 1 on FXR activity, nuclear translocation, and downstream targets was investigated in intestinal epithelial cells using various biochemical and cellular assays. Additionally, the photophysical properties of complex 1 were assessed for FXR imaging., Results: Complex 1 retained the desirable photophysical properties for monitoring FXR in intestinal cells while reversing OCA's activity from agonistic to antagonistic. It disrupted FXR-RXR heterodimerization, inhibited FXR nuclear translocation, and downregulated downstream targets responsible for bile acid absorption, transport, and metabolism in intestinal epithelial cells., Conclusion: The study successfully developed an imaging probe and modulator of FXR by conjugating OCA to an iridium(III) complex. Complex 1 retained the favorable photophysical properties of the iridium(III) complex, while reversing OCA's activity from agonistic to antagonistic. The findings highlight the exciting application of using metals to tailor the activity of nuclear receptor modulators in living systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ramie leaf polysaccharides (RLP) were extracted using deep eutectic solvent (DES) and microwave. The extraction conditions, i.e., buffer-to-substrate (B:S) ratio (10:1-30:1 w/v), microwave power (90-270 W) and extraction duration (2-4 min) were optimized using response surface methodology. Based on the optimized model, 21.1 mL/g B:S ratio, 263 W microwave power and 2.8 min extraction time had successfully produced RLP with 16.67 ± 1.10 % (w/w) yield and 80.84 ± 1.16 % 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The 23.4 ± 0.389 kDa RLP was a neutral polysaccharide with low carbohydrate, protein, and phenolic contents. The low galacturonic acid content (0.89 ± 0.05 mg/g) suggested RLP contained partially pectic-polysaccharide. The major monosaccharides of RLP were rhamnose, glucose, galactose and xylose. RLP was a relatively non-linear, highly branched polysaccharide with short branches based on the monosaccharide ratio. Bioactivity screening had identified the reduction (0.66 ± 0.02 mmol Fe 2+ /g) and copper chelation (48.5 ± 0.4 %) activities of RLP. The polysaccharide could also absorb ultraviolet (UV) in which it gave major protection against UVB with 8.7 ± 0.3 sun protection factor. These biological activities were related to specific functional groups, monosaccharide units, molecular weight and/or the neutral property of RLP. The current findings provided new insights into the antioxidant, copper chelation and sun protection benefit of RLP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cryptococcosis is the third most common invasive fungal infection in solid-organ transplant (SOT) recipients after candidiasis and aspergillosis. These patients are at risk of disseminated cryptococcosis because of immuosuppressive therapy. The median time to disease onset after kidney transplantation is approximately 35 months and it rarely occurs more than 10 years after transplantation. Herein, we report a case of 64-year-old kidney transplant recipient suffering from coexisting disseminated cryptococcosis with brain and skin involvement, together with cytomegalovirus (CMV) antigenemia more than 20 years after transplant. She presented with frontal headache and bilateral hand tremor, in addition to multiple nodular lesions over bilateral lower limbs. The diagnosis was made after lumbar puncture and skin biopsy. She was successfully treated with a course of anti-fungal and anti-CMV regimen without any relapse of central nervous system infection. Our case illustrates that disseminated cryptococcosis can occur very late after organ transplant. It is thus important to watch out for late-onset opportunistic infections and strike the balance between risks of infections and rejections in SOT patients., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

The cyclization of heteroatom-functionalized alkynes induced by d 6 -transition-metal centers has traditionally been associated with the vinylidene pathway. However, recent evidence suggests that d 6 -transition-metal centers can also activate alkynes through non-vinylidene pathways. In this study, we conducted a comprehensive experimental and theoretical investigation into the reactions between the Ru(II) complex [Ru([9]aneS3)(bpy)(OH 2 )] 2+ and 2-alkynylanilines. Our study revealed that the selectivity between the vinylidene and non-vinylidene pathways can be tuned by reaction temperature, substrate, and solvent polarity. This strategic control allows for the preferential formation of either C2- or C3-metalated indole zwitterion complexes. Additionally, we identified a rare decyclization mechanism that enables the conversion of C2-metalated indoles to C3-metalated indoles, underscoring the significance of product stability in these pathways. Overall, this work demonstrates practical approaches to control the preference between vinylidene and non-vinylidene pathways, which is crucial for the design of new catalysts and metalated heterocyclic complexes., (© 2024 Wiley-VCH GmbH.)

The optimal timing of rhinoplasty for patients with nasal bone fractures remains controversial. We investigated whether the timing of rhinoplasty after nasal trauma affects the aesthetic outcome of the procedure. A total of 41 adult patients with nasal bone fractures who underwent rhinoplasty between 2006 and 2021 were enrolled in this study. A visual analog scale (VAS) was used to indicate the assessor's satisfaction with the surgical outcome after a comparison of the pre- and postoperative facial photographs of each patient. Of the 41 patients, 28 underwent rhinoplasty within 14 days after nasal trauma (early rhinoplasty group), whereas 13 underwent rhinoplasty more than 14 days after nasal trauma (late rhinoplasty group). The rate of receiving spreader and shield graft was higher in the late rhinoplasty group ( p  = 0.043 and 0.018, respectively). Patients with type IV or V nasal bone fracture and patients with preoperative saddle noses had higher VAS scores than those with types I to III fractures and those without preoperative saddle nose ( p  = 0.003 and 0.020, respectively). There was no significant difference in overall aesthetic outcome between the early and late rhinoplasty groups. Both groups achieved significantly better radix height, dorsal height, and tip projection after rhinoplasty. The aesthetic outcome of rhinoplasty performed in the early posttrauma period is comparable with that of rhinoplasty performed more than 2 weeks after nasal bone fracture. Rhinoplasty can be considered a safe surgical treatment option for nasal bone fracture, even in the early posttrauma period. LEVEL OF EVIDENCE: : 4., Competing Interests: None declared., (Thieme. All rights reserved.)

A weak van der Waals (vdW) force in layered materials enables their isolation into thin flakes through mechanical exfoliation while sustaining their intrinsic electronic and optical properties. Here, we introduce a universal roll-printing method capable of producing vdW multilayer films on wafer-to-meter scale. This process uses sequential exfoliation and transfer of layered materials from the powder sources to target substrates through a repeated rolling of a cylindrical metal drum. We achieve uniformly coated films with a library of vdW powders on various mechanically rigid and flexible substrates. The printed films are configured into different devices including light-emitting diodes and photodetectors. The presented technique offers substantial benefits in terms of cost efficiency and a low thermal budget while offering high material quality.

Background: Primary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use., Methods: Clinical data including height, weight, diagnosis, treatment, and hormonal evaluations during follow-up were extracted from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Chemocog study (2007-2012), accompanied by data from two Australian, high-volume testicular cancer centres included in the iTestis testicular cancer registry (2012-2019). Low testosterone was defined by a serum concentration of testosterone (T) < 10 nmol/L, and was classified as primary by a serum concentration of luteinising hormone (LH) > 8 IU/L, otherwise as secondary., Results: Two hundred eighty-five individuals with either stage 1 or advanced testicular cancer were included. Of these, 105 (37%) were treated with orchidectomy and chemotherapy. Forty-nine (17%) met criteria for low testosterone during follow-up: 21 (43%) had primary and 27 (55%) had secondary low testosterone. Survivors of testicular cancer with higher body mass index were more likely to display low testosterone, both primary (p = 0.032) and secondary (p = 0.028). Our data did not show evidence of an association between older age or chemotherapy use and low testosterone in our cohort., Conclusions: Low total serum testosterone was common in survivors of testicular cancer, and associated with a higher body mass index prior to orchidectomy, suggesting that elevated body mass index may contribute to low testosterone in this population, and that body weight, diet, and exercise should be addressed in testicular cancer follow-up., (© 2024. The Author(s).)

In this study, we report the innovative application of whole-cell patch-clamp electrophysiology in assessing broad-spectrum neutralisation by three different antivenoms, of venoms from the medically significant scorpion genus Centruroides. Envenomations by as many as 21 species from the Centruroides genus result in up to 300,000 envenomations per year in Mexico, which poses significant and potentially life-threatening pathophysiology. We first evaluated the in vitro manifestation of envenomation against two human voltage-gated sodium (hNa V ) channel subtypes: hNa V 1.4 and hNa V 1.5, which are primarily expressed in skeletal muscles and cardiomyocytes, respectively. The neutralisation of venom activity was then characterised for three different antivenoms using a direct competition model against the more potent target, hNa V 1.4. While broad-spectrum neutralisation was identified, variation in neutralisation arose for Centruroides elegans, C. limpidus, C. noxius and C. suffusus venoms, despite the presence of a number of these venoms within the immunising mixture. This raises questions regarding the truly "broad" neutralisation capacity of the antivenoms. This study not only extends previous validation of the in vitro investigation of antivenom efficacy utilising the whole-cell patch-clamp technique but also underscores the potential of this animal-free model in exploring cross-reactivity, experimental scalability, and most importantly, informing clinical management practices regarding the administration of antivenom in Mexico., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bioactive peptides produced via enzymatic hydrolysis have been widely investigated for their dipeptidyl peptidase-IV (DPP-IV) inhibitory properties. However, deficit of studies on fermentation as a mean to produce DPP-IV inhibitory peptides prompted us to draw a comparative study on DPP-IV inhibitory peptides generated from cow, camel, goat, and sheep milk using probiotic fermentation. Further, peptide identification, in silico molecular interactions with DPP-IV, and ensemble docking were performed. Results obtained suggested that goat milk consistently exhibited higher hydrolysis than other milk types. Further, Pediococcus pentosaceus (PP-957) emerged as a potent probiotic, with significantly lower DPP-IV-IC 50 values 0.17, 0.12, and 0.25 µg/mL protein equivalent in fermented cow, camel, and goat milk, respectively. Overall, peptides (RPPPPVAM, CHNLDELKDTR, and VLSLSQPK) exhibited strong binding affinity with binding energies of -9.31, -9.18 and -8.9 Kcal·mol -1 , respectively, suggesting their potential role as DPP-IV inhibitors. Overall, this study, offers valuable information toward antidiabetic benefits of fermented milk products via inhibition of DPP-IV., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Despite the recent advances in understanding the mechanisms of olfaction, no tools are currently available to noninvasively identify loss of smell. Because of the substantial increase in patients presenting with coronavirus disease 2019-related loss of smell, the pandemic has highlighted the urgent need to develop quantitative methods. Methods: Our group investigated the use of a novel fluorescent probe named Tsp1a-IR800 P as a tool to diagnose loss of smell. Tsp1a-IR800 P targets sodium channel 1.7, which plays a critical role in olfaction by aiding the signal propagation to the olfactory bulb. Results: Intuitively, we have identified that conditions leading to loss of smell, including chronic inflammation and coronavirus disease 2019, correlate with the downregulation of sodium channel 1.7 expression in the olfactory epithelium, both at the transcript and at the protein levels. We demonstrated that lower Tsp1a-IR800 P fluorescence emissions significantly correlate with loss of smell in live animals-thus representing a potential tool for its semiquantitative assessment. Currently available methods rely on delayed subjective behavioral studies. Conclusion: This method could aid in significantly improving preclinical and clinical studies by providing a way to objectively diagnose loss of smell and therefore aid the development of therapeutic interventions., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Competing Interests: Conflict of interest: None declared.

In this work, we have found that a prenotched double-network (DN) hydrogel, when subjected to tensile loading in a pure-shear geometry, exhibits intriguing stick-slip crack dynamics. These dynamics synchronize with the oscillation of the damage (yielding) zone at the crack tip. Through manipulation of the loading rate and the predamage level of the brittle network in DN gels, we have clarified that this phenomenon stems from the significant amount of energy dissipation required to form the damage zone at the crack tip, as well as a kinetic contrast between the rapid crack extension through the yielding zone (slip process) and the slow formation of a new yielding zone controlled by the external loading rate (stick process)., Competing Interests: Competing interests statement:The authors declare no competing interest.

Aims: Currently, there is limited data on prognostic indicators after insertion of percutaneous ventricular assist device (PVAD) in the treatment of cardiogenic shock (CS). This study evaluated the prognostic role of cardiac power output (CPO) ratio, defined as CPO at 24 h divided by early CPO (30 min to 2 h), in CS patients after PVAD., Methods and Results: Consecutive CS patients from the QEH-PVAD Registry were followed up for survival at 90 days after PVAD. Among 121 consecutive patients, 98 underwent right heart catheterization after PVAD, with CPO ratio available in 68 patients. The CPO ratio and 24-h CPO, but not the early CPO post PVAD, were significantly associated with 90-day survival, with corresponding area under curve in ROC analysis of 0.816, 0.740, and 0.469, respectively. In multivariate analysis, only the CPO ratio and lactate level at 24 h remained as independent survival predictors. The CPO ratio was not associated with age, sex, and body size. Patients with lower CPO ratio had significantly lower coronary perfusion pressure, worse right heart indices, and higher pulmonary vascular resistance. A lower CPO ratio was also significantly associated with mechanical ventilation and higher creatine kinase levels in myocardial infarction patients., Conclusion: In post-PVAD patients, the CPO ratio outperformed the absolute CPO values and other haemodynamic metrics in predicting survival at 90 days. Such a proportional change of CPO over time, likely reflecting native heart function recovery, may help to guide management of CS patients post-PVAD., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest in real time. Ion channels play a fundamental role in cellular signalling, and they are implicated in diverse pathological conditions, making them an attractive target in the field of molecular imaging. Many venom peptides exhibit exquisite selectivity and potency towards ion channels, rendering them ideal agents for molecular imaging applications. In this review, we illustrate the use of fluorescently-labelled venom peptides for disease diagnostics and intraoperative imaging of brain tumours and peripheral nerves. Finally, we address challenges for the development and clinical translation of venom peptides as nerve-targeted imaging agents.

Introduction: Deep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&E-stained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied., Methodology: In this study, we assess the impact of cell label derivation on H&E model performance, with CD3 + T-cells in lung cancer tissues as a proof-of-concept. We compare two Pix2Pix generative adversarial network (P2P-GAN)-based virtual staining models: one trained with cell labels obtained from the same tissue section as the H&E-stained section (the 'same-section' model) and one trained on cell labels from an adjacent tissue section (the 'serial-section' model)., Results: We show that the same-section model exhibited significantly improved prediction performance compared to the 'serial-section' model. Furthermore, the same-section model outperformed the serial-section model in stratifying lung cancer patients within a public lung cancer cohort based on survival outcomes, demonstrating its potential clinical utility., Discussion: Collectively, our findings suggest that employing ground truth cell labels obtained through the same-section approach boosts immunophenotyping DL solutions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Azam, Wee, Väyrynen, Yim, Xue, Chua, Lim, Somasundaram, Tan, Takano, Chow, Khor, Lim, Yeong, Lau and Cai.)

Two-photon voltage imaging has long been heralded as a transformative approach capable of answering many long-standing questions in modern neuroscience. However, exploiting its full potential requires the development of novel imaging approaches well suited to the photophysical properties of genetically encoded voltage indicators. We demonstrate that parallel excitation approaches developed for scanless two-photon photostimulation enable high-SNR two-photon voltage imaging. We use whole-cell patch-clamp electrophysiology to perform a thorough characterization of scanless two-photon voltage imaging using three parallel illumination approaches and lasers with different repetition rates and wavelengths. We demonstrate voltage recordings of high-frequency spike trains and sub-threshold depolarizations from neurons expressing the soma-targeted genetically encoded voltage indicator JEDI-2P-Kv. Using a low repetition-rate laser, we perform multi-cell recordings from up to fifteen targets simultaneously. We co-express JEDI-2P-Kv and the channelrhodopsin ChroME-ST and capitalize on their overlapping two-photon absorption spectra to simultaneously evoke and image action potentials using a single laser source. We also demonstrate in vivo scanless two-photon imaging of multiple cells simultaneously up to 250 µm deep in the barrel cortex of head-fixed, anaesthetised mice., (© 2024. The Author(s).)

Lay Abstract: This research review looked at how well different psychological behavioral therapies help improve the behavior of autistic children during dental visits. The researchers studied 18 different studies and found that, on average, about 56% of autistic children were able to cooperate with a dental exam using an oral mirror during their first visit. The number increased to about 64% during their second visit. However, using visual pedagogies or teaching aids did not seem to make a big difference in how many children could accept the dental exams. The results for other psychological behavioral techniques were also inconsistent, including Treatment and Education of Autistic and related Communication-handicapped CHildren, Picture Exchange Communication System, Applied Behavior Analysis, video modeling, and distractions. Many of the studies were small and did not include a comparison group. They also did not consider factors like how severe the autism was, other conditions the children had, or their previous dental experiences. Because of these limitations, the evidence supporting the use of psychological behavioral techniques to improve dental visits for autistic children is limited and uncertain. More research with larger studies and proper control groups is needed to better understand this topic.

Inorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm 2 /(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 μs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill., (© 2024. The Author(s).)

Regular blood glucose monitoring and control is necessary for people with type 1 or advanced type 2 diabetes, yet diagnosing and treating patients with diabetes in an accurate, sustained and patient-friendly manner remains limited. Here, a glucose-responsive bifunctional nanosystem (PGOxMns) is constructed via one-pot biomineralisation of manganese dioxide with glucose oxidase and ε-poly-L-lysine. Under hyperglycaemic conditions, the cascade reactions that occur when glucose interacts with PGOxMns can trigger the production of Mn(II), which enhances the magnetic resonance imaging signal. Simultaneously, manganese dioxide catalyses the decomposition of toxic hydrogen peroxide into oxygen, which also maintains glucose oxidase (GOx) activity. In an in vivo model of diabetes, PGOxMns is used to monitor glucose levels (0-20 mm) and allowed identification of diabetic mice via T 1 -weighted MRI. Furthermore, PGOxMns is found to have a high insulin-loading capacity (83.6%), likely due to its positive charge. A single subcutaneous injection of insulin-loaded nanosystem (Ins-PGOxMns) into diabetic mice resulted in a rapid and efficient response to a glucose challenge and prolonged blood glucose level control (< 200 mg dL -1 ) for up to 50 h. Overall, this proof-of-concept study demonstrates the feasibility of using biomineralised nanosystems to develop patient-friendly strategies for glucose monitoring and control., (© 2024 Wiley‐VCH GmbH.)

Diabetes is a chronic, metabolic disease characterized by hyperglycemia resulting from either insufficient insulin production or impaired cellular response to insulin. Exopolysaccharides (EPS) produced by Lactobacillus spp. demonstrated promising therapeutic potential in terms of their anti-diabetic properties. Extraction and purification of EPS produced by Lactobacillus acidophilus and Limosilactobacillus reuteri were performed using ethanol precipitation, followed by alcohol/salt based aqueous two-phase system (ATPS). The purification process involved ethanol precipitation followed by an alcohol/salt-based ATPS. The study systematically investigated various purification parameters in ATPS, including ethanol concentration, type and concentration of ionic liquid, type and concentration of salt and pH of salt. Purified EPS contents from L. acidophilus (63.30 μg/mL) and L. reuteri (146.48 μg/mL) were obtained under optimum conditions of ATPS which consisted of 30 % (w/w) ethanol, 25 % (w/w) dipotassium hydrogen phosphate at pH 10 and 2 % (w/w) 1-butyl-3-methylimidazolium octyl sulfate. The extracted EPS content was determined using phenol sulphuric acid method. In α-amylase inhibition tests, the inhibitory rate was found to be 92.52 % (L. reuteri) and 90.64 % (L. acidophilus), while in α-glucosidase inhibition tests, the inhibitory rate was 73.58 % (L. reuteri) and 68.77 % (L. acidophilus), based on the optimized parameters selected in ATPS. These results suggest that the purified EPS derived from the postbiotics of Lactobacillus spp. hold promise as potential antidiabetic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Milk-derived peptides have emerged as a popular mean to manage various lifestyle disorders such as diabetes. Fermentation is being explored as one of the faster and efficient way of producing peptides with antidiabetic potential. Therefore, in this study, an attempt was made to comparatively investigate the pancreatic α-amylase (PAA) inhibitory properties of peptides derived from milk of different farm animals through probiotic fermentation. Peptide's identification was carried out using liquid chromatography-quadrupole time-of-flight mass spectrometry and inhibition mechanisms were characterized by molecular docking. Results obtained showed a PAA-IC 50 value (the amount of protein equivalent needed to inhibit 50% of enzymes) between 2.39 and 36.1 µg protein equivalent for different fermented samples. Overall, Pediococcus pentosaceus MF000957-derived fermented milk from all animals indicated higher PAA inhibition than other probiotic derived fermented milk (PAA-IC 50 values of 6.01, 3.53, 15.6, and 10.8 µg protein equivalent for bovine, camel, goat, and sheep fermented milk). Further, molecular docking analysis indicated that camel milk-derived peptide IMEQQQTEDEQQDK and goat milk-derived peptide DQHQKAMKPWTQPK were the most potent PAA inhibitory peptides. Overall, the study concluded that fermentation derived peptides may prove useful in for managing diabetes via inhibition of carbohydrate digesting enzyme PAA., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The well-being of the Chinese high school students linked to the National Higher Education Entrance Examination, known as gaokao, has been a spotlight education issue in China. This study employed self-determination theory and Bourdieu's sociocultural theory to examine the relationship between life satisfaction, educational hope, and parental support among Chinese high school students. A number of 3,810 high school students from eight schools in Jiangsu, China, completed a validated context-relevant questionnaire. Structural equation model analysis suggested that parental support significantly impacted students' life satisfaction and educational hope. Findings showed that parental intangible support in terms of providing information, advice, encouragement, praise, and care has a direct and significant impact on the life satisfaction of Chinese youth. The extent to which students attach importance to and put effort into achieving their educational aspirations, known as goal commitment, mediated the relationship between parental support and life satisfaction. Moreover, Chinese high school students' educational hope is shaped by their family. Parental support moderates goal commitment, which varies based on parental education background. In short, parents play a critical role in the growth and development of Chinese high school students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han and Yuen.)

Black phosphorus (BP) is a narrow bandgap (∼0.3 eV) semiconductor with a great potential for optoelectronic devices in the mid-infrared wavelength. However, it has been challenging to achieve a high-quality scalable BP thin film. Here we present the successful synthesis of optically active BP films on a centimeter scale. We utilize the pulsed laser deposition of amorphous red phosphorus, another allotrope of phosphorus, followed by a high-pressure treatment at ∼8 GPa to induce a phase conversion into BP crystals. The crystalline quality was improved through thermal annealing, resulting in the observation of photoluminescence emission at mid-infrared wavelengths. We demonstrate high-pressure conversion on a centimeter scale with a continuous film with a thickness of ∼18 nm using a flat-belt-type high-pressure apparatus. This synthesis procedure presents a promising route to obtain optical-quality BP films, enabling the exploration of integrated optoelectronic device applications such as light-emitting devices and mid-infrared cameras on a chip scale.

Cancer immunotherapy harnesses the immune system to combat tumors and has emerged as a major cancer treatment modality. The PD-1/PD-L1 immune checkpoint modulates interactions between tumor cells and T cells and has been extensively targeted in cancer immunotherapy. However, the monoclonal antibodies known to target this immune checkpoint have considerable side effects, and novel PD-1/PD-L1 inhibitors are therefore required. Herein, a peptide inhibitor to disrupt PD-1/PD-L1 interactions was designed through structure-driven phage display engineering coupled to computational modification and optimization. BetaPb , a novel peptide library constructed by using the known structure of PD-1/PD-L, was used to develop inhibitors against the immune checkpoint, and specific peptides with high affinity toward PD-1 were screened through enzyme-linked immunosorbent assays, homogeneous time-resolved fluorescence, and biolayer interferometry. A potential inhibitor, B8 , was preliminarily screened through biopanning. The binding affinity of B8 toward PD-1 was confirmed through computation-aided optimization. Assessment of B8 variants ( B8.1 , B8.2 , B8.3 , B8.4 , and B8.5 ) demonstrated their attenuation of PD-1/PD-L1 interactions. B8.4 exhibited the strongest attenuation efficiency at a half-maximal effective concentration of 0.1 μM and the strongest binding affinity to PD-1 (equilibrium dissociation constant = 0.1 μM). B8.4 outperformed the known PD-1/PD-L1 interaction inhibitor PL120131 in disrupting PD-1/PD-L1 interactions, revealing that B8.4 has remarkable potential for modification to yield an antitumor agent. This study provides valuable information for the future development of peptide-based drugs, therapeutics, and immunotherapies for cancer.

Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Insects and small animals often utilize structured surfaces to create friction during their movements. These surfaces typically consist of pillar-like fibrils that interact with a counter surface. Understanding the mechanical interaction between such surfaces is crucial for designing structured surfaces for engineering applications. In the first part of our study, we examined friction between poly(dimethylsiloxane) (PDMS) samples with surfaces patterned with pillar-arrays. We observed that sliding between these surfaces occurs through the interfacial glide of dislocation structures. The frictional force that resists this dislocation glide is a result of periodic single pillar-pillar contact and sliding. Hence, comprehending the intricate interaction between individual pillar contacts is a fundamental prerequisite for accurately modeling the friction behavior of the pillar array. In this second part of the study, we thoroughly investigated the contact interaction between two pillars located on opposite sides of an interface, with different lateral and vertical offsets. We conducted experiments using PDMS pillars to measure both the reaction shear and normal forces. Contact interaction between pillars was then studied using finite element (FE) simulations with the Coulomb friction model, which yielded results that aligned well with the experimental data. Our result offers a fundamental solution for comprehending how fibrillar surfaces contact and interact during sliding, which has broad applications in both natural and artificial surfaces.

Biology is replete with examples, at length scales ranging from the molecular (ligand-receptor binding) to the mesoscopic scale (wing arresting structures on dragonflies) where shape-complementary surfaces are used to control interfacial mechanical properties such as adhesion, friction, and contact compliance. Related bio-inspired and biomimetic structures have been used to achieve unique interfacial properties such as friction and adhesion enhancement, directional and switchable properties. The ability to tune friction by altering surface structures offers advantages in various fields, such as soft robotics and tire manufacturing. Here, we present a study of friction between polydimethylsiloxane (PDMS) samples with surfaces patterned with pillar-arrays. When brought in contact with each other the two samples spontaneously produce a Moiré pattern that can also be represented as an array of interfacial dislocations that depends on interfacial misorientation and lattice spacing. Misorientation alone produces an array of screw dislocations, while lattice mismatch alone produces an array of edge dislocations. Relative sliding motion is accompanied by interfacial glide of these patterns. The frictional force resisting dislocation glide arises from periodic single pillar-pillar contact and sliding. We study the behavior of pillar-pillar contact with larger (millimeter scale) pillar samples. Inter-pillar interaction measurements are combined with a geometric model for relative sliding to calculate frictional stress that is in good agreement with experiments.

Objectives: This study aimed to evaluate the sequential postoperative changes in tip aesthetics, by evaluating the aesthetic performance of the septal extension graft with or without tip grafting., Methods: A total of 62 patients who underwent rhinoplasty with tip plasty were included. Using a three-dimensional scanner, we measured anthropometric aesthetic features of the nasal tip, including tip height, tip width, nasolabial angle, and columellar lobular angle. Preoperative and 1-month and 12-month postoperative anthropometric parameters were compared. The patients were grouped according to surgical techniques (i.e., septal extension only and septal extension plus tip grafting groups) and subtype of tip graft., Results: The 1-month postoperative values of all four aesthetic features were significantly increased compared with the preoperative values. The tip height, tip width, and nasolabial angle at 12 months were significantly decreased compared with 1 month post-operation values, whereas the tip height and width were still greater than the preoperative values. No difference was found between 1 and 12 month values of columellar lobular angle. There were no differences in the degree of decrease in tip height, tip width, nasolabial angle, and columellar lobular angle between the septal extension graft only and septal extension graft plus tip graft groups. There were no differences in the tip graft by subtypes, single- and multi-layer tip grafts., Conclusions: Increased tip height, tip width, and widened nasolabial angle gained immediately after septal extension grafting surgery gradually decreased over the year regardless of addition of tip graft or tip grafting methods., Level of Evidence: 4 Laryngoscope, 134:678-683, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

In dairy science, camel milk (CM) constitutes a center of interest for scientists due to its known beneficial effect on diabetes as demonstrated in many in vitro, in vivo, and clinical studies and trials. Overall, CM had positive effects on various parameters related to glucose transport and metabolism as well as the structural and functional properties of the pancreatic β-cells and insulin secretion. Thus, CM consumption may help manage diabetes; however, such a recommendation will become rationale and clinically conceivable only if the exact molecular mechanisms and pathways involved at the cellular levels are well understood. Moreover, the application of CM as an alternative antidiabetic tool may first require the identification of the exact bioactive molecules behind such antidiabetic properties. In this review, we describe the advances in our knowledge of the molecular mechanisms reported to be involved in the beneficial effects of CM in managing diabetes using different in vitro and in vivo models. This mainly includes the effects of CM on the different molecular pathways controlling (1) insulin receptor signaling and glucose uptake, (2) the pancreatic β-cell structure and function, and (3) the activity of key metabolic enzymes in glucose metabolism. Moreover, we described the current status of the identification of CM-derived bioactive peptides and their structure-activity relationship study and characterization in the context of molecular markers related to diabetes. Such an overview will not only enrich our scientific knowledge of the plausible mode of action of CM in diabetes but should ultimately rationalize the claim of the potential application of CM against diabetes. This will pave the way toward new directions and ideas for developing a new generation of antidiabetic products taking benefits from the chemical composition of CM., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The overexpression and overactivation of epidermal growth factor receptor (EGFR) are frequently observed in human cancers, including squamous cell carcinoma and adenocarcinoma. In this study, a covalent EGFR probe was developed by conjugating afatinib to an iridium(III) scaffold. Complex 1 showed enhanced luminescence in living epidermoid squamous carcinoma A431 cells compared to other cell lines, via engaging EGFR as confirmed via CETSA and knockdown experiments. Moreover, complex 1 inhibited downstream targets of EGFR in cellulo with repression persisting after removal of the complex, indicating an irreversible mode of inhibition. Finally, complex 1 showed potent antiproliferative activity against A431 cells with comparable potency to afatinib alone. To our knowledge, complex 1 is the first EGFR covalent inhibitor based on an iridium scaffold reported in the literature, with the potential to be further explored as a theranostic agent in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

High synthesis temperatures and specific growth substrates are typically required to obtain crystalline or oriented inorganic functional thin films, posing a significant challenge for their utilization in large-scale, low-cost (opto-)electronic applications on conventional flexible substrates. Here, we explore a pulse irradiation synthesis (PIS) to prepare thermoelectric metal chalcogenide (e.g., Bi 2 Se 3 , SnSe 2 , and Bi 2 Te 3 ) films on multiple polymeric substrates. The self-propagating combustion process enables PIS to achieve a synthesis temperature as low as 150 °C, with an ultrafast reaction completed within one second. Beyond the photothermoelectric (PTE) property, the thermal coupling between polymeric substrates and bismuth selenide films is also examined to enhance the PTE performance, resulting in a responsivity of 71.9 V/W and a response time of less than 50 ms at 1550 nm, surpassing most of its counterparts. This PIS platform offers a promising route for realizing flexible PTE or thermoelectric devices in an energy-, time-, and cost-efficient manner., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is a major contributor to global mortality rates, but current treatment options have limitations. Advanced theranostics are needed to effectively integrate diagnosis and therapeutic of HCC. Glycyrrhetinic acid (GA) has abundant binding sites with glycyrrhetinic acid receptors (GA-Rs) on the surface of HCC cells and has also been reported to possess ligands with mitochondrial-targeting capability but with limited efficacy. Herein, we report a near-infrared (NIR) luminescent theranostic complex 1 through conjugating an iridium(III) complex to GA, which exhibits the desired photophysical properties and promotes mitochondrial-targeting capability. Complex 1 was selectively taken up by HepG2 liver cancer cells and was imaged within mitochondria with NIR emission. Complex 1 targeted mitochondria and opened mitochondrial permeability transition pores (MPTPs), resulting in ROS accumulation, mitochondrial damage, disruption of Bax/Bcl-2 equilibrium, and tumor cell apoptosis, resulting in significantly improved anticancer activity compared to GA. This work offers a methodology for developing multifunctional theranostic probes with amplified specificity and efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)