Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

Oral administration microrobots for drug delivery.

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magnetic-controlled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

Anomalous Structural Transformation of Cu(I) Clusters into Multifunctional CuAg Nanoclusters.

We report an anomalous structural transformation of a Cu(I) cluster into two different types of copper-silver (CuAg) alloy nanoclusters. Different from previous reports, we demonstrate that under specifically designed reaction conditions, the Ag-doping could induce a substantial growth of the starting Cu15 and a Ag13Cu20 nanocluster was obtained via the unexpected insertion of an Ag13 kernel inside the Cu(I)-S shell. Ag13Cu20 demonstrates high activity to initiate the photopolymerization of previously hard-to-print inorganic polymers in 3D laser microprinting. Interestingly, a slight modification of the reaction condition leads to the formation of another Ag18-xCuxS (8≤x) nanocluster templated by a central S2- anion, which possesses a unique electronic structure compared to conventional template-free CuAg nanoclusters. Overall, this work unveils the intriguing doping chemistry of Cu clusters, as well as their capability to create different types of alloy nanoclusters with previously unobtainable structures and multifunctionality.

Two-Orders-of-Magnitude Enhancement of Photoinitiation Activity via a Simple Surface Engineering of Metal Nanoclusters.

Development of high-performance photoinitiator is the key to enhance the printing speed, structure resolution and product quality in 3D laser printing. Here, to improve the printing efficiency of 3D laser nanoprinting, we investigate the underlying photochemistry of gold and silver nanocluster initiators under multiphoton laser excitation. Experimental results and DFT calculations reveal the high cleavage probability of the surface S-C bonds in gold and silver nanoclusters which generate multiple radicals. Based on this understanding, we design several alkyl-thiolated gold nanoclusters and achieve a more than two-orders-of-magnitude enhancement of photoinitiation activity, as well as a significant improvement in printing resolution and fabrication window. Overall, this work for the first time unveils the detailed radical formation pathways of gold and silver nanoclusters under multiphoton activation and substantially improves their photoinitiation sensitivity via surface engineering, which pushes the limit of the printing efficiency of 3D laser lithography.

Mechanical Performance of Copper-Nanocluster-Polymer Nanolattices.

A type of copper-nanocluster-polymer composites is reported and showcased that their 3D nanolattices exhibit a superior combination of high strength, toughness, deformability, resilience, and damage-tolerance. Notably, the strength and toughness of ultralight copper-nanocluster-polymer nanolattices in some cases surpass current best performers, including alumina, nickel, and other ceramic or metallic lattices at low densities. Additionally, copper-nanocluster-polymer nanolattices are super-resilient, crack-resistant, and one-step printed under ambient condition which can be easily integrated into sophisticated microsystems as highly effective internal protectors. The findings suggest that, unlike traditional nanocomposites, the laser-induced interface and the high fraction of ultrasmall Cu15 nanoclusters as crosslinking junctions contribute to the marked nonlinear elasticity of copper-nanocluster-polymer network, which synergizes with the lattice-topology effect and culminates in the exceptional mechanical performance.

Pediatric Pterygopalatine Fossa Schwannoma Presenting as Vision Loss: A Case Report and Literature Review.

Neurosynovial tumors, originating from Schwann cells within nerve sheaths, are benign entities, with 25% to 45% manifesting in the head and neck region. However, occurrences in the pterygopalatine fossa (PPF) are exceptionally rare, and only a handful of cases have been documented. In this report, we present the unique case of a 6-year-old child exhibiting a sizable soft tissue mass in the left PPF, extending into the inferior orbital fissure. The patient underwent successful intranasal endoscopic removal of PPF schwannoma utilizing the prelacrimal recess approach, with postoperative pathology confirming the diagnosis of schwannoma. Schwannomas within the PPF are particularly uncommon, and instances of such tumors in pediatric patients are even more exceptional. This case highlights the diagnostic and therapeutic challenges associated with PPF schwannomas in children, emphasizing the significance of a multidisciplinary approach for optimal management. In addition, a comprehensive literature review is presented to provide insights into the existing knowledge on this rare entity, further contributing to the understanding of pediatric PPF schwannomas.

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

BACKGROUND: Intracellular Ca2+ cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) is responsible for the sequestration of cytosolic Ca2+ into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear. METHODS: Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20flox mice with Myh6-Cre mice. Echocardiography, blood pressure measurements, Langendorff perfusion, histological analysis and immunohistochemistry, quantitative reverse transcription-PCR, Western blot analysis, electrophysiological measurements, and chromatin immunoprecipitation assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Specific ablation of ZBTB20 in cardiomyocyte led to a significant increase in basal myocardial contractile parameters both in vivo and in vitro, accompanied by an impairment in cardiac reserve and exercise capacity. Moreover, the cardiomyocytes lacking ZBTB20 showed an increase in sarcoplasmic reticular Ca2+ content and exhibited a remarkable enhancement in both SERCA2a activity and electrically stimulated contraction. Mechanistically, PLN expression was dramatically reduced in cardiomyocytes at the mRNA and protein levels by ZBTB20 deletion or silencing, and PLN overexpression could largely restore the basal contractility in ZBTB20-deficient cardiomyocytes. CONCLUSIONS: These data point to ZBTB20 as a fine-tuning modulator of PLN expression and SERCA2a activity, thereby offering new perspective on the regulation of basal contractility in the mammalian heart.

The Role of Prohibitin-2 in Diseases.

Prohibitin-2 (PHB2) is a conserved protein in mitochondria that regulates various biological processes, including cell cycle, proliferation, apoptosis, transcription, signal transduction, and mitochondrial ridge morphogenesis. Recently, there has been growing interest in the biological function of PHB2. This article primarily discusses the recent advances in the role of PHB2 in diseases.

Value of biplane transrectal ultrasonography plus micro-flow imaging in preoperative T staging and rectal cancer diagnosis in combination with CEA/CA199 and MRI.

BACKGROUND: Rectal cancer is one of the most common malignant tumors and has a high incidence rate and fatality rate. Accurate preoperative T staging of rectal cancer is critical for the selection of appropriate rectal cancer treatment. Various pre-operative imaging methods are available, and the identification of the most accurate method for clinical use is essential for patient care. We investigated the value of biplane transrectal ultrasonography (TRUS) combined with MFI in preoperative staging of rectal cancer and explored the value of combining TRUS plus MFI with CEA/CA199 and MRI. METHODS: A total of 87 patients from Daping Hospital with rectal cancer who underwent TRUS examination plus MFI were included. Grades of MFI were determined by Alder classification. Among the total patients, 64 underwent MRI and serum CEA/CA199 tests additionally within one week of TRUS. Pathological results were used as the gold standard for cancer staging. Concordance rates between TRUS, MRI, and CEA/CA199 for tumors at different stages were compared. RESULTS: There were no significant differences between the Alder classification and pathological T staging. The concordance rate of TRUS and MFI for rectal cancer T staging was 72.4% (K = 0.615, p < 0.001). Serum CEA and CA199 levels were significantly different in tumors at different stages and increased progressively by pathological stage (p < 0.001); the accuracy rate was 71.88% (K = 0.599, p < 0.001), while that of MRI was 51.56% (K = 0.303, p < 0.001), indicating that TRUS had higher consistency in the preoperative T staging of rectal cancer. The combination of TRUS, MRI, and CEA/CA199 yielded an accuracy rate of 90.6%, which was higher than that of any method alone. CONCLUSIONS: Preoperative T staging of rectal cancer from biplane TRUS plus MFI was highly consistent with postoperative pathological T staging. TRUS combined with MRI and serum CEA/CA199 had a greater value in the diagnosis of rectal cancer and a higher diagnostic rate than any examination alone.

Subcellular Expression Patterns of FKBP Prolyl Isomerase 10 (FKBP10) in Colorectal Cancer and Its Clinical Significance.

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as 'FKBP10-C' (concentrated), 'FKBP10-T' (transitional) and 'FKBP10-D' (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.

Robot Assisted Laparoscopy Combined with Thoracoscopy in the Treatment of Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus.

BACKGROUND: Facing the 0.7-22% incidence rate of hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT), there are usually no obvious symptoms and signs when the tumor thrombus completely blocks the IVCTT in the early stage.1.J Gastroenterol. 29:41-46;2.Hepatogastroenterology. 41:154-157;3.Clin Cardiol. 19:211-213; Once diagnosed, it is the end-stage manifestation without unified treatment for HCC with IVCTT, bringing poor prognosis. Without active treatment, the median survival time is only 3 months. Previous scholars believed that patients with IVCTT should not adopt active surgical treatment. With the advance of technology, active surgical treatment has significantly lengthened the survival time with IVCTT.4.Ann Surg Oncol. 20:914-22;5.World J Surg Oncol. 11:259;6.Hepatogastroenterology. 58:1694-1699; However, for patients with HCC and IVCTT, open surgery was always selected in the past by opening the diaphragm through the combined thoracoabdominal incision to block the superior and subhepatic vena cava, leading long incision and huge trauma. With the development of minimally invasive techniques, laparoscopy thoracoscopy has showed great advantages in the treatment of HCC with IVCTT. A patient underwent laparoscopic with thoracoscopic resection of tumor and cancer thrombectomy after neoadjuvant therapy and then survived after follow-up.7.Ann Surg Oncol. 29:5548-5549 Therefore, it used as a first reported case of robot-assisted laparoscopic with thoracoscopic treatment of HCC complicated inferior vena cava cancer thrombectomy. METHODS: A 41-year-old man had a liver space-occupying lesion discovered during his medical examination 2 months ago. The diagnosis of HCC with IVCTT was confirmed by enhanced CT and biopsy specimen in the first hospitalization. A combination of TACE, targeted therapy, and immunotherapy plan was applied for the patient after multidisciplinary treatment (MDT). Specifically, Lenvatinib was taken orally 8 mg daily and 160 mg of toripalimab was given intravenously every 3 weeks. His reexamination CT showed that the tumor was more advanced after 2 months of treatment. The surgical operation was performed based on comprehensive consideration. The patient was placed in the left lateral decubitus position, and a thoracoscopic prefabricated the inferior vena cava above diaphragm blocking device was pulled out of the incision. The patient was switched to a supine position with the head of the bed raised 30 degrees. The gallbladder was removed first after entering the abdominal cavity, then prefabricated first hilar blocking band. Sterile rubber glove edges and hemo-lock were used to fabricate the blocking device. The novel hepatic inflow occlusion device is a safe, reliable, and convenient technique that is associated with favorable perioperative outcomes and low risk of conversion.8.Surg Endosc. 34:2807-2813 The liver along the middle hepatic vein was cut to expose the anterior wall of the inferior vena cava, then prefabricated posterior inferior vena cava blocking belt and right hepatic vein blocking belt. Finally, the first portal of liver, right hepatic vein, retrohepatic inferior vena cava, and inferior vena cava above diaphragm were blocked in sequence, so that accomplishing tumor resection and thrombectomy of inferior vena cava. It should be emphasized that before the inferior vena cava is completely sutured, the retrohepatic inferior vena cava blocking device should be released to allow blood flow to flush the inferior vena cava. Moreover, transesophageal ultrasound is required to real-time monitor inferior vena cava blood flow and IVCTT. Some images of the operation are shown in Fig. 1. Fig. 1 (a) Layout of the trocar. ①Make a 3cm small incision between the right anterior axillary line and the midaxillary line, parallel to the fourth and fifth intercostal spaces; a puncture hole in the next intercostal space for endoscope; ②2cm above the intersection of umbilicus horizontal line and axillary front line; ③Intersection of right clavicular midline and umbilical horizontal line; ④Superior margin of umbilicus; ⑤The midpoint of '④ & ⑥'; ⑥2cm below the intersection of left clavicular midline and left costal margin. (b) Prefabricated the inferior vena cava blocking device above diaphragm by thoracoscopic. (c) The smooth tumor thrombus protruding into the inferior vena cava RESULTS: It took 475 min to finish the operation, and the loss of blood was estimated as 300 ml. The patient was discharged from hospital 8 days after the operation without postoperative complication. HCC was confirmed by postoperative pathology. CONCLUSIONS: Robot surgical system reduces the limitations of laparoscopic surgery by offering a stable three-dimensional view, 10-times-enlarged image, restored eye-hand axis, and excellent dexterity with the endowristed instruments, which has several advantages over open operation such as diminished blood loss, reduced morbidity, and shorter hospital stay.9.Chirurg. 88:7-11;10.BMC Surg. 11:2;11.Minerva Chir. 64:135-146; Furthermore, it could favor the operative feasibility of difficult resections reducing the conversion rate and playing a role to extend the indications of liver resection to minimally invasive approaches. It may provide new curative options in patients deemed inoperable with conventional surgery, such as HCC with IVCTT.12.Biosci Trends. 16:178-188;13.J Hepatobiliary Pancreat Sci. 29:1108-1123.

Boronic acid and fructose-1,6-diphosphate dual-functionalized highly hydrophilic Zr-MOF for HILIC enrichment of N-linked glycopeptides.

The HILIC enrichment is a greatly compatible strategy for the extraction of glycopeptides in proteomics. Herein, a boric acid and fructose-1,6-diphosphate (FDP) dual-functionalized Zr-based metal-organic framework material UIO-PBA&FDP (UIO is the abbreviation for the University of Oslo, and PBA is the abbreviation for carboxy phenylboronic acid) was synthesized, characterized with the desirable excellent hydrophilicity and thus was explored for the enrichment of N-linked glycopeptides utilizing the HILIC interaction between the glycopeptides and the hydrophilic UIO-PBA&FDP at a high level of ACN concentration. A total of 359 N-linked glycopeptides corresponding to 104 glycoproteins were identified from only 1 µL of digested human serum by the enrichment of UIO-PBA&FDP, which showed a superiorly high coverage of the identified glycopeptides. The dual hydrophilic functionalized UIO-PBA&FDP could be an efficient HILIC material for the enrichment of N-linked glycopeptides from complex biological samples.

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming.

Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we explored whether FGFR1 acted a therapeutic target in human T-cell acute lymphoblastic leukemia (T-ALL) and the molecular mechanisms underlying T-ALL cell resistance to FGFR1 inhibitors. We showed that FGFR1 was significantly upregulated in human T-ALL and inversely correlated with the prognosis of patients. Knockdown of FGFR1 suppressed T-ALL growth and progression both in vitro and in vivo. However, the T-ALL cells were resistant to FGFR1 inhibitors AZD4547 and PD-166866 even though FGFR1 signaling was specifically inhibited in the early stage. Mechanistically, we found that FGFR1 inhibitors markedly increased the expression of ATF4, which was a major initiator for T-ALL resistance to FGFR1 inhibitors. We further revealed that FGFR1 inhibitors induced expression of ATF4 through enhancing chromatin accessibility combined with translational activation via the GCN2-eIF2α pathway. Subsequently, ATF4 remodeled the amino acid metabolism by stimulating the expression of multiple metabolic genes ASNS, ASS1, PHGDH and SLC1A5, maintaining the activation of mTORC1, which contributed to the drug resistance in T-ALL cells. Targeting FGFR1 and mTOR exhibited synergistically anti-leukemic efficacy. These results reveal that FGFR1 is a potential therapeutic target in human T-ALL, and ATF4-mediated amino acid metabolic reprogramming contributes to the FGFR1 inhibitor resistance. Synergistically inhibiting FGFR1 and mTOR can overcome this obstacle in T-ALL therapy.

Distribution and survival outcomes of primary head and neck hematolymphoid neoplasms in older people: a population-based study.

Primary head and neck hematolymphoid neoplasms (PHNHLN) are defined as a series of hematolymphoid system-derived neoplasms which primarily emanate in head and neck region. Due to the rarity and absence of symptomatic specificity, PHNHLN is easily neglected. The objective of this study is to investigate demographics, pathological subtype distribution, anatomical location, survival outcomes and prognostic factors of PHNHLN among older patients aged ≥ 60. The individual patient information in our study was derived from Surveillance, Epidemiology and End Results database. Descriptive epidemiological methods were used to analyze the distribution of histologic subtypes and primary anatomical sites. Kaplan-Meier survival curves and log-rank test were conducted to evaluate the effect of variables on the prognosis. Cox hazard regression was conducted to identify the independent prognostic factors. The male-to-female ratio in most pathological subtypes was close to 1:1. The most common pathological subtype was diffuse large B-cell lymphoma. The most commonly involved sites outside the lymph nodes were salivary glands, especially parotid gland, followed by tonsil, thyroid gland and tongue. The prognosis of mature T- and NK-cell non-Hodgkin lymphoma (NHL) was bleaker than Hodgkin lymphoma, mature B-cell NHL and plasma cell neoplasm. Age at diagnosis, presence of second primary malignancy (SPM), pathological subtype, Ann-Arbor stage, chemotherapy and radiation were independent prognostic factors of overall survival. Our study comprehensively reported the subtype distribution, anatomical sites and survival outcomes of PHNHLN among older patients, improving understanding of this rare group of cancer entities.

Simultaneous enrichment optimization of glycopeptides and phosphopeptides with the highly hydrophilic DZMOF-FDP.

Protein glycosylation and phosphorylation play essential roles in biological systems. The crosstalk of both glycosylation and phosphorylation on one protein represents an unveiled biological function. To realize the analyses of both glycopeptides and phosphopeptides, a simultaneous enrichment method of N-glycopeptides, mono-phosphopeptides and multi-phosphopeptides was developed based on a multi-functional dual-metal centered zirconium metal-organic framework that provided multiple interactions for HILIC, IMAC, and MOAC for glycopeptides and phosphopeptides. Based on a careful optimization of sample loading and elution conditions for the simultaneous enrichment of glycopeptides and phosphopeptides with the zirconium metal-organic framework, a total of 1011 N-glycopeptides derived from 410 glycoproteins and 1996 phosphopeptides including 741 multi-phosphopeptides derived from 1189 phosphoproteins could be identified from a HeLa cell digest. The simultaneous enrichment approach for glycopeptides and mono-/multi-phosphopeptides demonstrates the great potential of the combined interactions for HILIC, IMAC, and MOAC in integrated post-translational modification proteomics research.

Solvent-mediated precipitating synthesis and optical properties of polyhydrido Cu13 nanoclusters with four vertex-sharing tetrahedrons.

Structurally defined metal nanoclusters facilitate mechanism studies and promote functional applications. However, precisely constructing copper nanoclusters remains a long-standing challenge in nanoscience. Developing new efficient synthetic strategies for Cu nanoclusters is highly desirable. Here, we propose a solvent-mediated precipitating synthesis (SMPS) to prepare Cu13H10(SR)3(PPh3)7 nanoclusters (H-SR = 2-chloro-4-fluorobenzenethiol). The obtained Cu13 nanoclusters are high purity and high yield (39.5%, based on Cu atom), proving the superiority of the SMPS method. The Cu13 nanoclusters were comprehensively studied via a series of characterizations. Single crystal X-ray crystallography shows that the Cu13 nanoclusters contain a threefold symmetry axis and the Cu13 kernel is protected by a monolayer of ligands, including PPh3 and thiolates. Unprecedentedly, the aesthetic Cu13 kernel is composed of four vertex-sharing tetrahedrons, rather than the common icosahedral or cuboctahedral M13. The intramolecular π⋯π interactions between thiolates and PPh3 on the surface contribute to the stable configuration. Furthermore, electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) revealed the existence of ten hydrides, including four types of hydrides. Density functional theory (DFT) calculations without simplifying the ligands simulated the location of the 10 hydrides in the crystal structure. Additionally, the steady-state ultraviolet-visible absorption and fluorescence spectra of the Cu13 nanoclusters exhibit unique optical absorbance and photoluminescence. The ultrafast relaxation dynamics were also studied via transient absorption spectroscopy, and the three decay components are attributed to the relaxation pathways of internal conversion, structural relaxation and radiative relaxation. This work provides not only a novel SMPS strategy to efficiently synthesize Cu13 nanoclusters, but also a better insight into the structural characteristics and optical properties of the Cu nanoclusters.

Eukaryotic Ribosomal Protein S5 of the 40S Subunit: Structure and Function.

The ribosomal protein RPS5 is one of the prime proteins to combine with RNA and belongs to the conserved ribosomal protein family. It plays a substantial role in the process of translation and also has some non-ribosome functions. Despite the enormous studies on the relationship between the structure and function of prokaryotic RPS7, the structure and molecular details of the mechanism of eukaryotic RPS5 remain largely unexplored. This article focuses on the structure of RPS5 and its role in cells and diseases, especially the binding to 18S rRNA. The role of RPS5 in translation initiation and its potential use as targets for liver disease and cancer are discussed.

Microgravity and immune cells.

The microgravity environment experienced during spaceflight severely impaired immune system, making astronauts vulnerable to various diseases that seriously threaten the health of astronauts. Immune cells are exceptionally sensitive to changes in gravity and the microgravity environment can affect multiple aspects of immune cells through different mechanisms. Previous reports have mainly summarized the role of microgravity in the classification of innate and adaptive immune cells, lacking an overall grasp of the laws that microgravity effects on immune cells at different stages of their entire developmental process, such as differentiation, activation, metabolism, as well as function, which are discussed and concluded in this review. The possible molecular mechanisms are also analysed to provide a clear understanding of the specific role of microgravity in the whole development process of immune cells. Furthermore, the existing methods by which to reverse the damage of immune cells caused by microgravity, such as the use of polysaccharides, flavonoids, other natural immune cell activators etc. to target cell proliferation, apoptosis and impaired function are summarized. This review will provide not only new directions and ideas for the study of immune cell function in the microgravity environment, but also an important theoretical basis for the development of immunosuppression prevention and treatment drugs for spaceflight.

Recognizing the Minimum Structural Units Driving the Crystallization of SAPO-34 in a Top-Down Process.

Recognizing the structure and nature of the nuclei for zeolites crystallization on an atomic level is of great importance, which can provide guidance on the control of crystallization kinetics and the rational synthesis of zeolites. However, it remains a long-standing challenge due to the difficulty in characterization of amorphous precursor with limited crystal nuclei. Herein, a top-down synthesis system was designed for SAPO-34 molecular sieve and well investigated. A clear precursor solution with abundant SAPO-34 crystal nuclei was obtained under a depolymerization-dominant condition. The species in the liquid precursor were identified by FT-ICR MS, solid-state MAS NMR and atomic pair distribution function analyses. In combination with various designed experiments, it is revealed that both the formation of small species containing Si-O-Al bonds and reaching a certain concentration, is crucial for driving the crystallization of SAPO-34, rather than structural units with specific spatial conformation. This work provides an important understanding on the (pre)nucleation of SAPO-34 and sheds light on the synthesis control of SAPO molecular sieves.

Impact of casein-to-whey protein ratio on gastric emptying, proteolysis, and peptidome profile of fermented milk during in vitro dynamic gastrointestinal digestion in preschool children.

The effects of casein-to-whey ratios (i.e., 4:1, 2:1, 1:1, 1:1.5) in fermented milk on gastric emptying, proteolysis and intestinal peptidome were investigated using an in vitro dynamic stomach-intestine system mimicking preschool children digestion. The gastric emptying rate varied insignificantly among the milk samples. After 120 min digestion, the protein digestibility was found in the range of 73.3-93.5 %, with the highest extent of proteolysis observed at a casein-to-whey ratio of 2:1 due to the fewest gastric protein aggregates and relatively abundant caseins. Intestinal peptides derived from caseins or whey proteins showed a positive correlation with their parent protein content. The most abundant bioactive whey peptides were found at casein-to-whey ratio of 1:1.5 after intestinal digestion. These findings demonstrated the importance of protein compositions in fermented milk on the gastrointestinal proteolysis and peptide release in vitro. This will be meaningful for future development of milk products that are more suitable for children.