BMP10 functions independently from BMP9 for the development of a proper arteriovenous network.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterized by the presence of arteriovenous malformation (AVM) in multiple organs. HHT is caused by mutations in genes encoding major constituents for transforming growth factor-ß (TGF-ß) family signaling: endoglin (ENG), activin receptor-like kinase 1 (ALK1), and SMAD4. The identity of physiological ligands for this ENG-ALK1 signaling pertinent to AVM formation has yet to be clearly determined. To investigate whether bone morphogenetic protein 9 (BMP9), BMP10, or both are physiological ligands of ENG-ALK1 signaling involved in arteriovenous network formation, we generated a novel Bmp10 conditional knockout mouse strain. We examined whether global Bmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control, Bmp9-KO, and Bmp9/10-double KO (dKO) mice. Bmp10-iKO and Bmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, while Bmp9-KO did not display any noticeable vascular defects. Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina of Bmp10-iKO and Bmp9/10-dKO mice was detected. Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar to Bmp10-iKO mice, but their phenotypes were more pronounced. Administration of BMP10 protein, but not BMP9 protein, prevented retinal AVM in Bmp9/10-dKO and endothelial-specific Eng-iKO mice. These data indicate that BMP10 is indispensable for the development of a proper arteriovenous network, whereas BMP9 has limited compensatory functions for the loss of BMP10. We suggest that BMP10 is the most relevant physiological ligand of the ENG-ALK1 signaling pathway pertinent to HHT pathogenesis.

Fugetaxis of Cell-in-Catalytic-Coat Nanobiohybrids in Glucose Gradients.

Manipulation and control of cell chemotaxis remain an underexplored territory despite vast potential in various fields, such as cytotherapeutics, sensors, and even cell robots. Herein is achieved the chemical control over chemotactic movement and direction of Jurkat T cells, as a representative model, by the construction of cell-in-catalytic-coat structures in single-cell nanoencapsulation. Armed with the catalytic power of glucose oxidase (GOx) in the artificial coat, the nanobiohybrid cytostructures, denoted as Jurkat[Lipo_GOx] , exhibit controllable, redirected chemotactic movement in response to d-glucose gradients, in the opposite direction to the positive-chemotaxis direction of naïve, uncoated Jurkat cells in the same gradients. The chemically endowed, reaction-based fugetaxis of Jurkat[Lipo_GOx] operates orthogonally and complementarily to the endogenous, binding/recognition-based chemotaxis that remains intact after the formation of a GOx coat. For instance, the chemotactic velocity of Jurkat[Lipo_GOx] can be adjusted by varying the combination of d-glucose and natural chemokines (CXCL12 and CCL19) in the gradient. This work offers an innovative chemical tool for bioaugmenting living cells at the single-cell level through the use of catalytic cell-in-coat structures.

Impact of intravesical administration of tranexamic acid on gross hematuria in the emergency department: A before-and-after study.

INTRODUCTION: Local applications of tranexamic acid (TXA) have been effective in treating various hemorrhagic conditions. In patients with gross hematuria, the main treatment in the emergency department (ED) is continuous bladder irrigation (CBI). However, CBI has no pharmacological effects except blood clot removal from dilution. The aim of this study was to evaluate the impact of the intravesical TXA injection before CBI. METHODS: This study was a before-and-after, retrospective, and single-center study. The target population was hematuria patients who received CBI via a 3-way Foley catheter. As the intervention procedure, 1000 mg of TXA was injected through the Foley catheter and after 15 min, the Foley catheter was declamped and CBI started. Since the intervention started in March 2022, the patients from March 2022 to August 2022 were assigned to the after group and the patients from March 2021 to August 2021 were assigned to the before group. The primary outcomes were the length of stay in the ED and duration of Foley catheter placement. The secondary outcomes were the admissions and the revisits for CBI within 48 h after discharge. RESULTS: The numbers of patients in the before group and after group were 73 and 86, respectively. The median length of stay in the ED was shorter in the intervention group than in the group not treated with TXA (274 min vs. 411 mins, P < 0.001). The median duration of Foley catheter placement was also shorter in the intervention group than not treated with TXA (145 min vs. 308 mins, P < 0.001). The revisits after ED discharge were lower in the after group than in the before group (2.3% vs. 12.3%, P = 0.031). There was a trend for lower admissions in the TXA treatment group than before group (29.1% vs. 45.2%, P = 0.052). CONCLUSION: After the TXA intervention, reduction in the length of stay in the ED, the duration of Foley catheter placement, and the revisits after ED discharge was observed.

Application of Nanoparticles and Melatonin for Cryopreservation of Gametes and Embryos.

Cryopreservation of gametes and embryos, a technique widely applied in human infertility clinics and to preserve desirable genetic traits of livestock, has been developed over 30 years as a component of the artificial insemination process. A number of researchers have conducted studies to reduce cell toxicity during cryopreservation using adjuvants leading to higher gamete and embryo survival rates. Melatonin and Nanoparticles are novel cryoprotectants and recent studies have investigated their properties such as regulating oxidative stresses, lipid peroxidation, and DNA fragmentation in order to protect gametes and embryos during vitrification. This review presented the current status of cryoprotectants and highlights the novel biomaterials such as melatonin and nanoparticles that may improve the survivability of gametes and embryos during this process.

Aberrant role of ALK in tau proteinopathy through autophagosomal dysregulation.

Proteinopathy in neurodegenerative diseases is typically characterized by deteriorating activity of specific protein aggregates. In tauopathies, including Alzheimer's disease (AD), tau protein abnormally accumulates and induces dysfunction of the affected neurons. Despite active identification of tau modifications responsible for tau aggregation, a critical modulator inducing tau proteinopathy by affecting its protein degradation flux is not known. Here, we report that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, is crucial for the tau-mediated AD pathology. ALK caused abnormal accumulation of highly phosphorylated tau in the somatodendritic region of neurons through its tyrosine kinase activity. ALK-induced LC3-positive axon swelling and loss of spine density, leading to tau-dependent neuronal degeneration. Notably, ALK activation in neurons impaired Stx17-dependent autophagosome maturation and this defect was reversed by a dominant-negative Grb2. In a Drosophila melanogaster model, transgenic flies neuronally expressing active Drosophila Alk exhibited the aggravated tau rough eye phenotype with retinal degeneration and shortened lifespan. In contrast, expression of kinase-dead Alk blocked these phenotypes. Consistent with the previous RNAseq analysis showing upregulation of ALK expression in AD [1], ALK levels were significantly elevated in the brains of AD patients showing autophagosomal defects. Injection of an ALK.Fc-lentivirus exacerbated memory impairment in 3xTg-AD mice. Conversely, pharmacologic inhibition of ALK activity with inhibitors reversed the memory impairment and tau accumulation in both 3xTg-AD and tauC3 (caspase-cleaved tau) transgenic mice. Together, we propose that aberrantly activated ALK is a bona fide mediator of tau proteinopathy that disrupts autophagosome maturation and causes tau accumulation and aggregation, leading to neuronal dysfunction in AD.

In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells.

(‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal-if not scientific or clinical-evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies of CBD actions on neural cells, the neuroprotective capability of CBD on primary neurons with the suggested operating actions is discussed, followed by the reported CBD actions on glia and the CBD-induced regeneration from neural stem cells. A summary section gives a general overview of the biochemical actions of CBD on neural cells, with a future perspective. This review will provide a basic and fundamental, but crucial, insight on the mechanistic understanding of CBD actions on neural cells in the brain, at the molecular level, and the therapeutic potential of CBD in the prevention and treatment of neurological diseases, although to date, there seem to have been relatively limited research activities and reports on the cell culture-level, in vitro studies of CBD effects on primary neural cells.

Fabrication and Characterization of Neurocompatible Ulvan-Based Layer-by-Layer Films.

Construction of extracellular matrix-mimetic nanofilms has considerable potential in biomedical and nanomedicinal fields. In this work, we fabricated neurocompatible layer-by-layer (LbL) films based on ulvan (ULV), a highly sulfated polysaccharide having compositional similarity to glycosaminoglycans that play important functional roles in the brain. ULV was durably assembled as a film with chitosan, another marine-derived polysaccharide, and the film enabled the stable adhesion of primary hippocampal neurons with high viability, comparable to the conventional poly-d-lysine surface. Notably, the ULV-based LbL films accelerated neurite outgrowth and selectively suppressed the adhesion of astrocytes, highlighting its potential as an advanced platform for neural implants and devices.

Enzymatically degradable, starch-based layer-by-layer films: application to cytocompatible single-cell nanoencapsulation.

The build-up and degradation of cytocompatible nanofilms in a controlled fashion have great potential in biomedical and nanomedicinal fields, including single-cell nanoencapsulation (SCNE). Herein, we report the fabrication of biodegradable films of cationic starch (c-ST) and anionic alginate (ALG) by electrostatically driven layer-by-layer (LbL) assembly technology and its application to the SCNE. The [c-ST/ALG] multilayer nanofilms, assembled either on individual Saccharomyces cerevisiae or on the 2D flat gold surface, degrade on demand, in a cytocompatible fashion, via treatment with α-amylase. Their degradation profiles are investigated, while systematically changing the α-amylase concentration, by several surface characterization techniques, including quartz crystal microbalance with dissipation monitoring (QCM-D) and ellipsometry. DNA incorporation in the LbL nanofilms and its controlled release, upon exposure of the nanofilms to an aqueous α-amylase solution, are demonstrated. The highly cytocompatible nature of the film-forming and -degrading conditions is assessed in the c-ST/ALG-shell formation and degradation of S. cerevisiae. We envisage that the cytocompatible, enzymatic degradation of c-ST-based nanofilms paves the way for developing advanced biomedical devices with programmed dissolution in vivo.

Application of intraoperative lung-protective ventilation varies in accordance with the knowledge of anaesthesiologists: a single-Centre questionnaire study and a retrospective observational study.

BACKGROUND: The benefits of lung-protective ventilation (LPV) with a low tidal volume (6 mL/kg of ideal body weight [IBW]), limited plateau pressure (< 28-30 cm H2O), and appropriate positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome have become apparent and it is now widely adopted in intensive care units. Recently evidence for LPV in general anaesthesia has been accumulated, but it is not yet generally applied by anaesthesiologists in the operating room. METHODS: This study investigated the perception about intraoperative LPV among 82 anaesthesiologists through a questionnaire survey and identified the differences in ventilator settings according to recognition of lung-protective ventilation. Furthermore, we investigated the changes in the trend for using this form of ventilation during general anaesthesia in the past 10 years. RESULTS: Anaesthesiologists who had received training in LPV were more knowledgeable about this approach. Anaesthesiologists with knowledge of the concept behind LPV strategies applied a lower tidal volume (median (IQR [range]), 8.2 (8.0-9.2 [7.1-10.3]) vs. 9.2 (9.1-10.1 [7.6-10.1]) mL/kg; p = 0.033) and used PEEP more frequently (69/72 [95.8%] vs. 5/8 [62.5%]; p = 0.012; odds ratio, 13.8 [2.19-86.9]) for laparoscopic surgery than did those without such knowledge. Anaesthesiologists who were able to answer a question related to LPV correctly (respondents who chose 'height' to a multiple choice question asking what variables should be considered most important in the initial setting of tidal volume) applied a lower tidal volume in cases of laparoscopic surgery and obese patients. There was an increase in the number of patients receiving LPV (VT < 10 mL/kgIBW and PEEP ≥5 cm H2O) between 2004 and 2014 (0/818 [0.0%] vs. 280/818 [34.2%]; p <  0.001). CONCLUSIONS: Our study suggests that the knowledge of LPV is directly related to its implementation, and can explain the increase in LPV use in general anaesthesia. Further studies should assess the impact of using intraoperative LPV on clinical outcomes and should determine the efficacy of education on intraoperative LPV implementation.

Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model.

In neurodegenerative diseases like AD, tau forms neurofibrillary tangles, composed of tau protein. In the AD brain, activated caspases cleave tau at the 421th Asp, generating a caspase-cleaved form of tau, TauC3. Although TauC3 is known to assemble rapidly into filaments in vitro, a role of TauC3 in vivo remains unclear. Here, we generated a transgenic mouse expressing human TauC3 using a neuron-specific promoter. In this mouse, we found that human TauC3 was expressed in the hippocampus and cortex. Interestingly, TauC3 mice showed drastic learning and spatial memory deficits and reduced synaptic density at a young age (2-3months). Notably, tau oligomers as well as tau aggregates were found in TauC3 mice showing memory deficits. Further, i.p. or i.c.v. injection with methylene blue or Congo red, inhibitors of tau aggregation in vitro, and i.p. injection with rapamycin significantly reduced the amounts of tau oligomers in the hippocampus, rescued spine density, and attenuated memory impairment in TauC3 mice. Together, these results suggest that TauC3 facilitates early memory impairment in transgenic mice accompanied with tau oligomer formation, providing insight into the role of TauC3 in the AD pathogenesis associated with tau oligomers and a useful AD model to test drug candidates.

OCIAD2 activates γ-secretase to enhance amyloid ß production by interacting with nicastrin.

The gamma (γ)-secretase holoenzyme is composed of four core proteins and cleaves APP to generate amyloid beta (Aß), a key molecule that causes major neurotoxicity during the early stage of Alzheimer's disease (AD). However, despite its important role in Aß production, little is known about the regulation of γ-secretase. OCIAD2, a novel modulator of γ-secretase that stimulates Aß production, and which was isolated from a genome-wide functional screen using cell-based assays and a cDNA library comprising 6,178 genes. Ectopic expression of OCIAD2 enhanced Aß production, while reduction of OCIAD2 expression suppressed it. OCIAD2 expression facilitated the formation of an active γ-secretase complex and enhanced subcellular localization of the enzyme components to lipid rafts. OCIAD2 interacted with nicastrin to stimulate γ-secretase activity. OCIAD2 also increased the interaction of nicastrin with C99 and stimulated APP processing via γ-secretase activation, but did not affect Notch processing. In addition, a cell-permeable Tat-OCIAD2 peptide that interfered with the interaction of OCIAD2 with nicastrin interrupted the γ-secretase-mediated AICD production. Finally, OCIAD2 expression was significantly elevated in the brain of AD patients and PDAPP mice. This study identifies OCIAD2 as a selective activator of γ-secretase to increase Aß generation.

Neuropathogenic role of adenylate kinase-1 in Aß-mediated tau phosphorylation via AMPK and GSK3ß.

Abnormally hyperphosphorylated tau is often caused by tau kinases, such as GSK3ß and Cdk5. Such occurrence leads to neurofibrillary tangle formation and neuronal degeneration in tauopathy, including Alzheimer's disease (AD). However, little is known about the signaling cascade underlying the pathologic phosphorylation of tau by Aß(42). In this study, we show that adenylate kinase 1 (AK1) is a novel regulator of abnormal tau phosphorylation. AK1 expression is markedly increased in the brains of AD patients and AD model mice and is significantly induced by Aß(42) in the primary neurons. Ectopic expression of AK1 alone augments the pathologic phosphorylation of tau at PHF1, CP13 and AT180 epitopes and enhances the formation of tau aggregates. Inversely, downregulation of AK1 alleviates Aß(42)-induced hyperphosphorylation of tau. AK1 plays a role in Aß(42)-induced impairment of AMPK activity and GSK3ß activation in the primary neurons. Pharmacologic studies show that treatment with an AMPK inhibitor activates GSK3ß, and a GSK3ß inhibitor attenuates AK1-mediated tau phosphorylation. In a Drosophila model of human tauopathy, the retinal expression of human AK1 severely exacerbates rough eye phenotype and increases abnormal tau phosphorylation. Further, neural expression of AK1 reduces the lifespan of tau transgenic files. Taken together, these observations indicate that the neuronal expression of AK1 is induced by Aß(42) to increase abnormal tau phosphorylation via AMPK-GSK3ß and contributes to tau-mediated neurodegeneration, providing a new upstream modulator of GSK3ß in the pathologic phosphorylation of tau.

Enhanced intrapulmonary delivery of anticancer siRNA for lung cancer therapy using cationic ethylphosphocholine-based nanolipoplexes.

Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.

Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin.

Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them in accessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells over expressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells.

The moderating role of circadian gene polymorphisms in the relationship between sleep disturbance and circulating lymphocyte subsets in colorectal cancer patients.

AIM: We investigated the impact of sleep disturbance on immune status in colorectal cancer (CRC) patients with consideration of the moderating role of circadian clock gene polymorphisms. METHODS: A prospective longitudinal study design was used to collect information regarding sleep disturbance. Blood samples for immunologic assays were obtained the day before the first (baseline) and last cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical sleep disturbance was compared between the two-time points using the Pittsburgh Sleep Quality Index (PSQI) global score. We analysed single-nucleotide polymorphisms in rs2278749, rs3749474, rs2291738, rs17031614, and rs2287161. The dependent variables included changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two-time points. The results were analysed using moderated regression analysis; the p-values were adjusted using the false discovery rate. RESULTS: Among the 104 patients, no significant dyadic associations were observed between changes in lymphocyte percentages and the PSQI global score. However, the moderated regression analysis revealed five significant associations (rs2287161 with CD8+, rs2278749 and rs2291738 with CD19+, and rs17031614 with CD4+ and CD16/56+ lymphocytes). The inclusion of each interaction resulted in a significant increase (5.7-10.7%) in the variance explained by changes in lymphocyte percentage. CONCLUSION: Patients with specific circadian gene allele types may be more susceptible to immune dysregulation when experiencing sleep disturbances. Considering that sleep disturbance is a modifiable factor that can impact immune regulation, it is essential to prioritise the management of sleep disturbances in CRC patients receiving FOLFOX chemotherapy.

Current Status of Flow Cytometric Immunophenotyping of Hematolymphoid Neoplasms in Korea.

Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCI-HLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey. We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positive/negative criteria, and reporting. Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positive/negative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. Conclusions: This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Strategic design of gold nanocatalysts for effective photocatalytic organic transformation.

We demonstrate the design strategy of free-standing Au nanocatalysts by correlating their physicochemical characteristics with photocatalytic performance. By tailoring the particle size and surface characteristics, we found that small Au nanocatalysts called Au nanoclusters with discrete energy levels are more effective than large metallic Au nanoparticles, while the microenvironments (e.g., charge status and hydrophilicity/hydrophobicity) around the surface of Au-nanoclusters are crucial in determining the performance. With the optimized Au nanocatalyst, under visible light, decarboxylative radical addition reactions for C-C bond formation (i.e., Giese reaction) were first achieved with high yields and further utilized for the preparation of one of the bioactive γ-aminobutyric acid derivatives, pregabalin (Lyrica®), demonstrating its potential in pharmaceutical applications.