Highly selective Zn2+ near-infrared fluorescent probe and its application in biological imaging.

Zn2+ plays a vital role in regulating various life processes, such as gene expression, cell signaling, and brain function. In this study, a near-infrared fluorescent probe AXS was synthesized to detect Zn2+ with good fluorescence specificity, high selectivity, and high sensitivity; the detection limit of Zn2+ was 6.924 × 10-11 M. The mechanism of Zn2+ recognition by the AXS probe was investigated by 1H nuclear magnetic resonance titrations, UV-visible spectroscopy, fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and high-resolution mass spectrometry. Test paper experiments showed that the AXS probe could detect Zn2+ in real samples. In addition, quantitative and qualitative detection of Zn2+ in common foodstuffs was achieved. For portable Zn2+ detection, a smartphone detection platform was also developed based on the AXS probe. Importantly, the AXS probe showed good bioimaging capabilities in Caenorhabditis elegans and mice.

Covalent Organic Frameworks Based Electrocatalysts for Two-Electron Oxygen Reduction Reaction: Design Principles, Recent Advances, and Perspective.

Hydrogen peroxide (H2O2) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e-) of the oxygen reduction reaction (ORR) for H2O2 production has attracted much attention due to its eco-friendly nature and operational simplicity in contrast to the conventional anthraquinone process. The challenge is to design electrocatalysts with high activity and selectivity and to understand their structure-activity relationship and catalytic mechanism in the ORR process. Covalent organic frameworks (COFs) provide an efficient template for the construction of highly efficient electrocatalysts due to their designable structure, excellent stability, and controllable porosity. This review firstly outlines the design principles of COFs, including the selection of metallic and nonmetallic active sites, the modulation of the electronic structure of the active sites, and the dimensionality modulation of the COFs, to provide guidance for improving the production performance of H2O2. Subsequently, representative results are summarized in terms of both metallic and metal-free sites to follow the latest progress. Moreover, the challenges and perspectives of 2e- ORR electrocatalysts based on COFs are discussed.

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis.

BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

Large-Scale Fabrication of Stable Silicon Anode in Air for Sulfide Solid State Batteries via Ionic-Electronic Dual Conductive Binder.

The construction of a continuous ionic/electronic pathway is critical for Si-based sulfide all-solid-state batteries (ASSBs) with the advantages of high-energy density and high-cycle stability. However, a significant impediment arises from the parasitic reaction occurring between the ionic sulfide solid-state electrolyte and electronic carbon additive, posing a formidable challenge. Additionally, the fabrication of electrodes necessitates stringent operational conditions, further limiting practical applicability. Herein, an ionic-electronic dual conductive binder for the fabrication of robust silicon anode under ambient air conditions in the absence of high-cost and air-sensitive sulfide solid-state electrolyte for ASSBs is reported. This binder incorporates in situ reduced silver nanoparticles into a high-strength polymer rich in ether bonds, establishing a conductive pathway for lithium ions and electrons. With the binder-composited Si anode, the half-cell exhibits a remarkable capacity of 1906.9 mAh g-1 and stable cycling for 500 cycles at a current density of 2 C (4.4 mA cm-2) under a low stack pressure of 5 MPa. The full cell using Ni0.9Co0.075Mn0.025O2 (NCM90) exhibits a remark cycling stability within 2000 cycles at 5 C (8 mA cm-2). This work presents an inspired design of functional binders for large-scale manufacture and mild operation in a low-cost way for Si anodes in ASSBs.

Selenium-Doped Nanoheterojunctions for Highly Efficient Cancer Radiosensitization.

Exploring efficient and low-toxicity radiosensitizers to break through the bottleneck of radiation tolerance, immunosuppression and poor prognosis remains one of the critical developmental challenges in radiotherapy. Nanoheterojunctions, due to their unique physicochemical properties, have demonstrated excellent radiosensitization effects in radiation energy deposition and in lifting tumor radiotherapy inhibition. Herein, they doped selenium (Se) into prussian blue (PB) to construct a nano-heterojunction (Se@PB), which could promote the increase of Fe2+/Fe3+ ratio and conversion of Se to a high valence state with Se introduction. The Fe2+-Se-Fe3+ electron transfer chain accelerates the rate of electron transfer on the surface of the nanoparticles, which in turn endows it with efficient X-ray energy transfer and electron transport capability, and enhances radiotherapy physical sensitivity. Furthermore, Se@PB induces glutathione (GSH) depletion and Fe2+ accumulation through pro-Fenton reaction, thereby disturbs the redox balance in tumor cells and enhances biochemical sensitivity of radiotherapy. As an excellent radiosensitizer, Se@PB effectively enhances X-ray induced mitochondrial dysfunction and DNA damage, thereby promotes cell apoptosis and synergistic cervical cancer radiotherapy. This study elucidates the radiosensitization mechanism of Se-doped nanoheterojunction from the perspective of the electron transfer chain and biochemistry reaction, which provides an efficient and low-toxic strategy in radiotherapy.

Neural Network Inspired Binder Enables Fast Li-Ion Transport and High Stress Adaptation for Si Anode.

Extensive investigations have proven the effectiveness of elastic binders in settling the challenge of structural damage posed by volume expansion of high-capacity anode used in nanoscale silicon. However, the sluggish ionic conductivity of polymer binder severely restricts the electrode reactions, making it unsuitable for practical applications. Inspired by the biological tissues with rapid neurotransmission and robust muscles, we propose a biomimetic binder that contains ionic conductive polymer (by polymerization reaction of poly(ethylene glycol) diglycidyl ether and polyethylenimine) and rigid polymer backbone (polyacrylic acid), which can effectively mitigate both Li-ion transport resistance and lithiation stress to stabilize the silicon nanoparticles during cycles. Consequently, the silicon anode with biomimetic binder achieves a rate capability of 1897 mAh g-1 at 8.0 A g-1 and capacity retention of 87% after 150 cycles under areal capacity upon 3.0 mAh cm-2. These results demonstrate the possibility of decoupling ionic conductivity from mechanical properties toward practical high-capacity anodes for energy-dense batteries.

Longitudinal Analysis of Humoral and Cellular Immune Response up to 6 Months after SARS-CoV-2 BA.5/BF.7/XBB Breakthrough Infection and BA.5/BF.7-XBB Reinfection.

The rapid mutation of SARS-CoV-2 has led to multiple rounds of large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes of humoral and cellular immunity responses to several subvariants after infection remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera and 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, and IFN-γ secreting CD4+/CD8+ T cell response to several SARS-CoV-2 variants, we observed that each component of immune response exhibited distinct kinetics. Either BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection induces relatively high level of binding and neutralizing antibody titers against Omicron subvariants at an early time point, which rapidly decreases over time. Most of the individuals at 6 months post-breakthrough infection completely lost their neutralizing activities against BQ.1.1, CH.1.1, BA.2.86, JN.1 and XBB subvariants. Individuals with BA.5/BF.7-XBB reinfection exhibit immune imprinting shifting and recall pre-existing BA.5/BF.7 neutralization antibodies. In the BA.5 breakthrough infection group, the frequency of BA.5 and XBB.1.16-RBD specific memory B cells, resting memory B cells, and intermediate memory B cells gradually increased over time. On the other hand, the frequency of IFN-γ secreting CD4+/CD8+ T cells induced by WT/BA.5/XBB.1.16 spike trimer remains stable over time. Overall, our research indicates that individuals with breakthrough infection have rapidly declining antibody levels but have a relatively stable cellular immunity that can provide some degree of protection from future exposure to new antigens.

Synergetic regulation of SEI mechanics and crystallographic orientation for stable lithium metal pouch cells.

The advancement of Li-metal batteries is significantly impeded by the presence of unstable solid electrolyte interphase and Li dendrites upon cycling. Herein, we present an innovative approach to address these issues through the synergetic regulation of solid electrolyte interphase mechanics and Li crystallography using yttrium fluoride/polymethyl methacrylate composite layer. Specifically, we demonstrate the in-situ generation of Y-doped lithium metal through the reaction of composite layer with Li metal, which reduces the surface energy of the (200) plane, and tunes the preferential crystallographic orientation to (200) plane from conventional (110) plane during Li plating. These changes effectively passivate Li metal, thereby significantly reducing undesired side reactions between Li and electrolytes by 4 times. Meanwhile, the composite layer with suitable modulus (~1.02 GPa) can enhance mechanical stability and maintain structural stability of SEI. Consequently, a 4.2 Ah pouch cell with high energy density of 468 Wh kg-1 and remarkable capacity stability of 0.08% decay/cycle is demonstrated under harsh condition, such as high-areal-capacity cathode (6 mAh cm-2), lean electrolyte (1.98 g Ah-1), and high current density (3 mA cm-2). Our findings highlight the potential of reactive composite layer as a promising strategy for the development of stable Li-metal batteries.

Identifying ADHD-Related Abnormal Functional Connectivity with a Graph Convolutional Neural Network.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is characterized by inattention, hyperactivity, and impulsivity. The neural mechanisms underlying ADHD remain inadequately understood, and current approaches do not well link neural networks and attention networks within brain networks. Our objective is to investigate the neural mechanisms related to attention and explore neuroimaging biological tags that can be generalized within the attention networks. In this paper, we utilized resting-state functional magnetic resonance imaging data to examine the differential functional connectivity network between ADHD and typically developing individuals. We employed a graph convolutional neural network model to identify individuals with ADHD. After classification, we visualized brain regions with significant contributions to the classification results. Our results suggest that the frontal, temporal, parietal, and cerebellar regions are likely the primary areas of dysfunction in individuals with ADHD. We also explored the relationship between regions of interest and attention networks, as well as the connection between crucial nodes and the distribution of positively and negatively correlated connections. This analysis allowed us to pinpoint the most discriminative brain regions, including the right orbitofrontal gyrus, the left rectus gyrus and bilateral insula, the right inferior temporal gyrus and bilateral transverse temporal gyrus in the temporal region, and the lingual gyrus of the occipital lobe, multiple regions of the basal ganglia and the upper cerebellum. These regions are primarily involved in the attention executive control network and the attention orientation network. Dysfunction in the functional connectivity of these regions may contribute to the underlying causes of ADHD.

Acoustic Metagrating Holograms.

Metasurface holograms represent a common category of metasurface devices that utilize in-plane phase gradients to shape wavefronts, forming holographic images through the application of the generalized Snell's law (GSL). While conventional metasurfaces focus solely on phase gradients, metagratings, which incorporate higher-order wave diffraction, further expand the GSL's generality. Recent advances in certain acoustic metagratings demonstrate an updated GSL extension capable of reversing anomalous transmission and reflection, whose reversal is characterized by the parity of the number of wave propagation trips through the metagrating. However, the current extension of GSL remains limited to 1D metagratings, unable to access 2D holographic images in 3D spaces. Here, the GSL extension to 2D metagratings for manipulating waves within 3D spaces is investigated. Through this analysis, a series of acoustic metagrating holograms is experimentally demonstrated. These holographic images exhibit the unique ability to switch between transmission and reflection types independently. This study introduces an additional dimension to modern holography design and metasurface wavefront manipulation.

Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

A near-infrared fluorescent ratiometric probe with large Stokes shift for multi-mode sensing of Pb2+ and bioimaging.

Pb2+ is a heavy metal ion pollutant that poses a serious threat to human health and ecosystems. The conventional methods for detecting Pb2+ have several limitations. In this study, we introduce a novel fluorescent probe that enables the detection of Pb2+ in the near-infrared region, free from interference from other common ions. A unique characteristic of this probe is its ability to rapidly and accurately identify Pb2+ through ratiometric measurements accompanied by a large Stokes shift of 201 nm. The limit of detection achieved by probe was remarkably low, surpassing the standards set by the World Health Organization, and outperforming previously reported probes. To the best of our knowledge, this is the first organic small-molecule fluorescent probe with both near-infrared emission and ratiometric properties for the detection of Pb2+. We present a triple-mode sensing platform constructed using a probe that allows for the sensitive and selective recognition of Pb2+ in common food items. Furthermore, we successfully conducted high-quality fluorescence imaging of Pb2+ in various samples from common edible plants, HeLa cells, Caenorhabditis elegans, and mice. Importantly, the probe-Pb2+ complex exhibited tumour-targeting capabilities. Overall, this study presents a novel approach for the development of fluorescent probes for Pb2+ detection.

Enhanced Recovery of Oil Mixtures from Calcite Nanopores Facilitated by CO2 Injection.

Slow production, preferential recovery of light hydrocarbons, and low recovery factors are common challenges in oil production from unconventional reservoirs dominated by nanopores. Gas injection-based techniques such as CO2 Huff-n-Puff have shown promise in addressing these challenges. However, a limited understanding of the recovery of oil mixtures on the nanopore scale hinders their effective optimization. Here, we use molecular dynamics simulations to study the recovery of an oil mixture (C10 + C19) from a single 4 nm-wide calcite dead-end pore, both with and without CO2 injection. Without CO2 injection, oil recovery is much faster than expected from oil vaporization and features an undesired selectivity, i.e., the preferential recovery of lighter C10. With CO2 injection, oil recovery is accelerated and its selectivity toward C10 is greatly mitigated. These recovery behaviors are understood by analyzing the spatiotemporal evolution of C10, C19, and CO2 distributions in the calcite pore. In particular, we show that interfacial phenomena (e.g., the strong adsorption of oil and CO2 on pore walls, their competition, and their modulation of transport behavior) and bulk phenomena (e.g., solubilization of oil by CO2 in the middle portion of the pore) play crucial roles in determining the oil recovery rate and selectivity.

Decoding emotion with phase-amplitude fusion features of EEG functional connectivity network.

Decoding emotional neural representations from the electroencephalographic (EEG)-based functional connectivity network (FCN) is of great scientific importance for uncovering emotional cognition mechanisms and developing harmonious human-computer interactions. However, existing methods mainly rely on phase-based FCN measures (e.g., phase locking value [PLV]) to capture dynamic interactions between brain oscillations in emotional states, which fail to reflect the energy fluctuation of cortical oscillations over time. In this study, we initially examined the efficacy of amplitude-based functional networks (e.g., amplitude envelope correlation [AEC]) in representing emotional states. Subsequently, we proposed an efficient phase-amplitude fusion framework (PAF) to fuse PLV and AEC and used common spatial pattern (CSP) to extract fused spatial topological features from PAF for multi-class emotion recognition. We conducted extensive experiments on the DEAP and MAHNOB-HCI datasets. The results showed that: (1) AEC-derived discriminative spatial network topological features possess the ability to characterize emotional states, and the differential network patterns of AEC reflect dynamic interactions in brain regions associated with emotional cognition. (2) The proposed fusion features outperformed other state-of-the-art methods in terms of classification accuracy for both datasets. Moreover, the spatial filter learned from PAF is separable and interpretable, enabling a description of affective activation patterns from both phase and amplitude perspectives.

Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination.

The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.

How close are we to a breakthrough? The hunt for blood biomarkers in Parkinson's disease diagnosis.

Parkinson's disease (PD), being the second largest neurodegenerative disease, poses challenges in early detection, resulting in a lack of timely treatment options to effectively manage the disease. By the time clinical diagnosis becomes possible, more than 60% of dopamine neurons in the substantia nigra (SN) of patients have already degenerated. Therefore, early diagnosis or identification of warning signs is crucial for the prompt and timely beginning of the treatment. However, conducting invasive or complex diagnostic procedures on asymptomatic patients can be challenging, making routine blood tests a more feasible approach in such cases. Numerous studies have been conducted over an extended period to search for effective diagnostic biomarkers in blood samples. However, thus far, no highly effective biomarkers have been confirmed. Besides classical proteins like α-synuclein (α-syn), phosphorylated α-syn and oligomeric α-syn, other molecules involved in disease progression should also be given equal attention. In this review, we will not only discuss proposed biomarkers that are currently under investigation but also delve into the mechanisms underlying the disease, focusing on processes such as α-syn misfolding, intercellular transmission and the crossing of the blood-brain barrier (BBB). Our aim is to provide an updated overview of molecules based on these processes that may potentially serve as blood biomarkers.

Comparative efficacy of 2% minoxidil alone against combination of 2% minoxidil and low-level laser therapy in female pattern hair loss-A randomized controlled trial in Chinese females.

OBJECTIVES: To investigate the effectiveness and safety of combination of 655 nm low level laser helmet device with topical 2 % minoxidil solution at FPHL in Chinese population. MATERIALS AND METHODS: Randomized, parallel, controlled, single-blind clinical trial was conducted. FPHL subjects were randomly allocated into 2 % minoxidil group and combination group. The 2 % minoxidil group received 1 ml topical 2 % minoxidil solution twice daily for 24 weeks. The combination group received 1 ml topical 2 % minoxidil solution twice daily together with 20 min 655 nm low-level laser helmet once every other day for 24 weeks. Hair parameters in two scalp areas including midscalp and vertex were evaluated at baseline, 12th week and 24th week. RESULTS: In midscalp area, the combination group showed a lower increase in intermediate hair percentage than 2 % minoxidil group, which was statistically significant. Besides, the combination group had statistically significant increase than 2 % minoxidil group in mean hair diameter. Reported relative adverse events included slightly hair loss (27.8 %), desquamation (19.0 %), pruritus (15.2 %), seborrhea (2.5 %) and hypertrichosis (2.5 %). CONCLUSION: In our trial, LLLT was demonstrated as a useful supplementary treatment for FPHL and the combination with 2 % minoxidil accomplished better improvement in intermediate hair enlargement and hair diameter of midscalp for FPHL.

Clinicopathologic and trichoscopic features of keratosis follicularis spinulosa decalvans: A case series study.

Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-linked hereditary disorder characterized by the triad of follicular hyperkeratosis-photophobia-alopecia. The clinical heterogeneity makes the diagnosis difficult. To investigate the clinicopathologic and trichoscopic features of KFSD and to further clarify the essential requisites for the diagnosis, we conducted a retrospective study of patients with KFSD. The clinical information, histologic features, and trichoscopic findings were evaluated. Eight patients were from seven separate families. Two females were mother and daughter from the same family and the other six patients were male and represented sporadic cases. The average age of onset of alopecia was 21.25 years. Involvement of the scalp hairs leading to progressive scarring alopecia on the midline of the scalp with variable degrees of inflammation was the pathognomonic feature. It typically began after puberty. Vellus hair-associated follicular hyperkeratosis affected all of the patients. However, photophobia was not a constant feature. Histopathologic examination revealed disorders of the hair follicle with an acute-chronic inflammatory response. Follicular changes including fused infundibulum, the protrusion of the outer root sheath into the follicular canal, and a dilatation of the follicles at the isthmus level caused by the occlusion of keratin were observed. The trichoscopic features included perifollicular scaling, tufted hairs, and loss of follicular openings. In conclusion, terminal hair involvement, either scalp hairs, eyebrows, or eyelashes, and the hyperkeratosis of the follicle of vellus hairs is the diagnostic basis of KFSD. We hypothesize that follicular changes in histopathology are the primary event that trigger variable inflammation and further follicular destruction.

The platelet storage lesion, what are we working for?

BACKGROUND: Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the technology for platelet preparation and storage has evolved over the decades, there are still challenges in the demand for platelets in blood banks because the platelet shelf life is limited to 5 days due to bacterial contamination and platelet storage lesions (PSLs) at 20-24°C under constant horizontal agitation. In addition, the relations between some adverse effects of platelet transfusions and PSLs have also been considered. Therefore, understanding the mechanisms of PSLs is conducive to obtaining high quality platelets and facilitating safe and effective platelet transfusions. OBJECTIVE: This review summarizes developments in mechanistic research of PSLs and their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms "PSL" and "platelet transfusion." The obtained literature was then roughly categorized based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies have explored PSLs from various perspectives, including changes in platelet morphology, surface molecules, biological response modifiers (BMRs), metabolism, and proteins and RNA, in an attempt to monitor PSLs and identify intervention targets that could alleviate PSLs. Moreover, novel platelet storage conditions, including platelet additive solutions (PAS) and reconsidered cold storage methods, are explored. There are two approaches to obtaining high-quality platelets. One approach simulates the in vivo environment to maintain platelet activity, while the other keeps platelets at a low activity level in vitro under low temperatures. CONCLUSION: Understanding PSLs helps us identify good intervention targets and assess the therapeutic effects of different PSLs stages for different patients.

Enhanced neutralization of SARS-CoV-2 variant BA.2.86 and XBB sub-lineages by a tetravalent COVID-19 vaccine booster.

Emerging SARS-CoV-2 sub-lineages like XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3 and the variant BA.2.86 have recently been identified. Understanding the efficacy of current vaccines on these emerging variants is critical. We evaluate the serum neutralization activities of participants who received COVID-19 inactivated vaccine (CoronaVac), those who received the recently approved tetravalent protein vaccine (SCTV01E), or those who had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Neutralization profiles against a broad panel of 30 sub-lineages reveal that BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibit heightened resistance to neutralization compared to previous variants. However, despite their extra mutations, BA.2.86 and the emerging XBB sub-lineages do not demonstrate significantly increased resistance to neutralization over XBB.1.5. Encouragingly, the SCTV01E booster consistently induces higher neutralizing titers against all these variants than breakthrough infection does. Cellular immunity assays also show that the SCTV01E booster elicits a higher frequency of virus-specific memory B cells. Our findings support the development of multivalent vaccines to combat future variants.