Comparison of outcomes between stent retriever combined with contact aspiration versus contact aspiration alone in patients without hyperdense artery sign/susceptibility vessel sign.

PURPOSE: To examine the relationship between hyperdense artery sign/susceptibility vessel sign (HAS/SVS) and thrombus composition, and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior-circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive acute anterior-circulation LVO patients (75 [63.1%] male; median age, 66 years) who underwent thrombectomy, and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was respectively assessed in noncontrast computed tomography (NCCT) and susceptibility-weighted imaging (SWI). Association of first-line thrombectomy techniques [stent retriever combined with contact aspiration (SR+CA) versus contact aspiration (CA)] with outcomes was assessed by the HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS(-), and 69 (67.0%) chose first-line SR+CA. Higher relative densities of fibrin/platelets (0.56 vs. 0.51, p<0.001) and lower relative densities of erythrocytes (0.32 vs. 0.42, p<0.001) were observed in HAS/SVS(-) than HAS/SVS(+) patients. First-line SR+CA was associated with reduced odds of distal embolization (aOR, 0.18; 95% CI, 0.04-0.83; p=0.027) and a more favorable 90-day functional outcome (aOR, 5.29; 95% CI, 1.06-26.34; p=0.042) in HAS/SVS(-) patients, and a longer recanalization time (53 min vs. 25 min, p=0.025) and higher risk of subarachnoid hemorrhage (24.2% vs. 0%, p=0.044) in HAS/SVS(+) patients. CONCLUSIONS: HAS/SVS(-) may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR+CA may have a possible better performance than CA in acute LVO patients without HAS/SVS.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Single-Atom Iron Doped Carbon Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Detection of MicroRNAs.

Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.

Smartphone-based colorimetric detection platform using color correction algorithms to reduce external interference.

Smartphone-based digital image colorimetry is a powerful, fast, low-cost approach to detecting target analytes. However, lighting conditions and camera parameters easily affect the detection results, significantly curtailing its applicability in multiple scenarios. In this study, an Android-based mobile application (SMP-CC) is developed, which offers a comprehensive package that includes image acquisition, color correction, and colorimetric analysis functions. Using a custom color card, a built-in algorithm in SMP-CC can minimize the color difference between the standard color block image captured by different smartphones under different lighting conditions and the standard value by an LS171 colorimeter less than 4.36. The algorithm significantly eliminates the impacts of external lighting conditions and differences in cell phone models. Furthermore, the feasibility of SMP-CC was verified by successful colorimetric detection of urine pH, glucose, and protein, demonstrating its potential in smartphone-based digital image colorimetry.

Lamprey--an excellent model for iron metabolism.

After 500 million years of evolution, lamprey is in a natural environment characterized by low temperature and high iron content, and its unique adaptive evolution mode has developed its organizational structure and life mechanism in the process of metamorphosis, which provides a new direction for people to further study the origin and evolution of life. Iron is one of the essential nutrients for the human body and plays an important role in metabolic processes, but when exceeded, it can lead to iron toxicity. For example, the serum iron concentration of pre-metamorphosis larvae is 149 times that of normal males, and the iron content in the liver of juveniles is about 2-3 times that of normal humans. Lamprey has a complete biochemical system to tolerate high concentrations of free iron in the body, and high expression of important genes for iron homeostasis, such as transferrin, ferritin heavy chain, superoxide dismutase, etc., improves iron transport, iron storage and antioxidant capacity. Lamprey has an IRE/IRP regulatory system, which is an important protection mechanism for lamprey to adapt to the high iron content environment in the organization. In addition, lampreys gradually form oral glands during metamorphosis and development, which become the unique iron metabolism organs of lampreys. In this review, we mainly summarize the distribution of iron in various tissues of lamprey and the potential mechanism of adapting to the content of iron in the body, so as to provide a theoretical basis for the subsequent search for the molecular mechanism of iron metabolism.

Effect of electroacupuncture at "Neiguan" (PC6) on pain and brain orexin 1 receptor in mice with inflammatory pain. / 电针"å† å ³"å¯¹ç‚Žæ€§ç—›å°é¼ è„‘å† é£Ÿæ¬²ç´ 1受体的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC6) on pain response in mice injected with complete Freund's adjuvant (CFA) in the hind paw, so as to investigate the mechanism of orexin 1 receptor (OX1R) -endogenous cannabinoid 1 receptor (CB1R) pathway in acupuncture analgesia. METHODS: A total of 48 male C57BL/6 mice were used in the present study. In the first part of this study, 18 mice were randomized into control, model and EA groups, with 6 mice in each group. In the second part of this study, 30 mice were randomized into control, model, EA, EA+Naloxone, EA+OX1R antagonist (SB33486) groups, with 6 mice in each group. Inflammatory pain model was established by subcutaneous injection of 20 µL CFA solution in the left hind paw. EA (2 Hz, 2 mA ) was applied to bilateral PC6 for 20 min, once a day for 5 consecutive days. The mice in the EA+Naloxone and EA+SB33486 groups were intraperitoneally injected with naloxone (10 mg/kg) or SB33486 (15 mg/kg) 15 min before EA intervention on day 5, respectively. Tail-flick method and Von Frey method were used to detect the thermal pain threshold and mechanical pain threshold of mice. Quantitative real-time PCR was used to detect the expression level of ß-endorphin mRNA in periaqueductal gray (PAG) of mice. The expression of OX1R positive cells in the lateral hypothalamic area (LH) and CB1R positive cells in the ventrolateral periaqueductal gray (vlPAG) were detected by immunofluorescence. RESULTS: Compared with the control group, the thermal pain threshold and mechanical pain threshold of the model group were decreased (P<0.001), the expression level of ß-endorphin mRNA in PAG was decreased (P<0.001), and the numbers of OX1R positive cells in LH and CB1R positive cells in vlPAG were decreased (P<0.05, P<0.001). Compared with the model group, the thermal pain threshold and mechanical pain threshold of the EA group were significantly increased (P<0.001), and the numbers of OX1R positive cells in LH and CB1R positive cells in vlPAG were increased (P<0.01, P<0.001). Compared with the EA group, the mechanical pain threshold in the EA+SB33486 group was significantly decreased (P<0.01), but there was no significant difference in the mechanical pain threshold between the EA+Naloxone group and EA group, and the numbers of OX1R positive neurons in LH and CB1R positive neurons in vlPAG were decreased in the EA+SB33486 group (P<0.001). CONCLUSIONS: EA at PC6 can achieve analgesic effect on CFA mice by activating the OX1R-CB1R pathway in the brain, and this effect is opioid-independent.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

Case reports on uniparental disomy of chromosomes 6 and 3 in paternity testing.

In paternity testing, when there are Mendelian errors in the alleles between the child and the parents, a slippage mutation, or silent allele may not fully explain the phenomenon. Sometimes, it is attributed to chromosomal abnormalities, such as uniparental disomy (UPD). Here, we present the investigation of two cases of suspected UPD in paternity testing based on short tandem repeat (STR) detection (capillary electrophoresis platform). Case 1 involves a trio, where all genotypes detected on chromosome 6 in the child are homozygous and found in the father. Case 2 is a duo (mother and child), where all genotypes on chromosome 3 in the child are homozygous and not always found in the mother. At the same time, Mendelian error alleles were also observed at specific loci in these two chromosomes. Furthermore, we used the MGIEasy Signature Identification Library Prep Kit for sequencing on the massively parallel sequencing platform, which included common autosomal, X and Y chromosomes, and mitochondrial genetic markers used in forensic practice. The results showed that the genotypes of shared STRs on the two platforms were consistent, and STRs and single nucleotide polymorphisms (SNPs) on these two chromosomes were homozygous. All other genetic markers followed the laws of inheritance. A comprehensive analysis supported the parent-child relationship between the child and the alleged parent, and the observed genetic anomalies can be attributed to UPD. UPD occurrences are rare, and ignoring its presence can lead to erroneous exclusions in paternity testing, particularly when multiple loci on a chromosome exhibit homozygosity.

The effect of body mass index on stroke prognosis: a systematic review and meta-analysis of 32 cohort studies with 330353 patients.

BACKGROUND: Many studies have explored the impact of body mass index (BMI) on stroke prognosis, yet findings remain inconsistent. AIMS: The aims of this study were to conduct a systematic review and meta-analyses to summarize the existing evidence on BMI and stroke outcomes. METHODS: PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, Wanfang Database and VIP Database were systematically searched from inception to Jan.1st, 2023. Cohort studies were included if they reported on a population of patients with stroke, evaluated BMI on stroke outcomes (mortality/recurrence/score of mRs) and reported original data. Data extraction and quality assessment were independently undertaken by two reviewers. Stata 16.0 software was used for meta-analysis. RESULTS: 32 studies involving 330,353 patients (5 Chinese language articles) were included in the analysis. The proportion of underweight, overweight, and obese patients was 1.85%, 18.2%, and 15.6%, respectively. Compared with normal weight, being underweight was associated with an increased risk of mortality (RR 1.78, 95% CI 1.60-1.96), poor functional outcomes defined as modified Rankin scale ≥3 (RR 1.33, 95% CI 1.22-1.45), and stroke recurrence (RR 1.19, 95% CI 1.04-1.37). Being overweight but not obese was associated with reduced mortality (RR 0.81, 95% CI 0.74-0.89) and better functional outcomes (RR 0.92, 95% CI 0.89-0.96), but did not alter the risk of stroke recurrence (RR 1.03, 95% CI 0.90-1.17). Obesity was associated with lower risk of mortality (RR 0.76, 95% CI 0.72-0.81), and better functional outcomes (RR 0.89, 95% CI 0.84-0.94). CONCLUSIONS: Our findings indicate that in patients with stroke, being underweight is associated with an increased risk of mortality, poor functional outcomes, and stroke recurrence. In contrast, being overweight but not obese, or being obese, was associated with a decreased risk of mortality and better functional outcomes. This are consistent with the obesity paradox in stroke, whereby obesity increases stroke risk in the general population but is associated with improved outcome in patients suffering stroke.Key Words body mass index; stroke; prognosis; meta-analysis.

Stepwise Toward Pure Blue Organic Light-Emitting Diodes by Synergetically Locking and Shielding Carbonyl/Nitrogen-Based MR-TADF Emitters.

Deep-blue multi-resonance (MR) emitters with stable and narrow full-width-at-half-maximum (FWHM) are of great importance for widening the color gamut of organic light-emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen-based MR core. Intramolecularly locking carbonyl/nitrogen-based bears narrower emission of 2,10-dimethyl-12,12-diphenyl-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione in solution and further with peripheral-shielding groups, deep-blue emitter (12,12-diphenyl-2,10-bis(9-phenyl-9H-fluoren-9-yl)-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione, DPQAO-F) exhibits ultra-pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO-F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper-device of DPQAO-F exhibits a record-high EQEmax of 32.7% in the deep-blue region, representing the first example of carbonyl/nitrogen-based OLED that can concurrently achieve narrow bandwidth in the deep-blue region and a high electroluminescent efficiency surpassing 30%.

Unraveling the role of C1GALT1 in abnormal glycosylation and colorectal cancer progression.

C1GALT1 plays a pivotal role in colorectal cancer (CRC) development and progression through its involvement in various molecular mechanisms. This enzyme is central to the O-glycosylation process, producing tumor-associated carbohydrate antigens (TACA) like Tn and sTn, which are linked to cancer metastasis and poor prognosis. The interaction between C1GALT1 and core 3 synthase is crucial for the synthesis of core 3 O-glycans, essential for gastrointestinal health and mucosal barrier integrity. Aberrations in this pathway can lead to CRC development. Furthermore, C1GALT1's function is significantly influenced by its molecular chaperone, Cosmc, which is necessary for the proper folding of T-synthase. Dysregulation in this complex interaction contributes to abnormal O-glycan regulation, facilitating cancer progression. Moreover, C1GALT1 affects downstream signaling pathways and cellular behaviors, such as the epithelial-mesenchymal transition (EMT), by modifying O-glycans on key receptors like FGFR2, enhancing cancer cell invasiveness and metastatic potential. Additionally, the enzyme's relationship with MUC1, a mucin protein with abnormal glycosylation in CRC, highlights its role in cancer cell immune evasion and metastasis. Given these insights, targeting C1GALT1 presents a promising therapeutic strategy for CRC, necessitating further research to develop targeted inhibitors or activators. Future efforts should also explore C1GALT1's potential as a biomarker for early diagnosis, prognosis, and treatment response monitoring in CRC, alongside investigating combination therapies to improve patient outcomes.

Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Structuring restricted amorphous molecular chains in the reinforced cellulose film by uniaxial stretching.

The construction of the preferred orientation structure by stretching is an efficient strategy to fabricate high-performance cellulose film and it is still an open issue whether crystalline structure or amorphous molecular chain is the key factor in determining the enhanced mechanical performance. Herein, uniaxial stretching with constant width followed by drying in a stretching state was carried out to cellulose hydrogels with physical and chemical double cross-linking networks, achieving high-performance regenerated cellulose films (RCFs) with an impressive tensile strength of 154.5 MPa and an elastic modulus of 5.4 GPa. The hierarchical structure of RCFs during uniaxial stretching and drying was systematically characterized from micro- to nanoscale, including microscopic morphology, crystalline structure as well as relaxation behavior at a molecular level. The two-dimensional correlation spectra of dynamic mechanical analysis and Havriliak-Negami fitting results verified that the enhanced mechanical properties of RCFs were mainly attributed to the stretch-induced tight packing and restricted relaxation of amorphous molecular chains. The new insight concerning the contribution of molecular chains in the amorphous region to the enhancement of mechanical performance for RCFs is expected to provide valuable guidance for designing and fabricating high-performance eco-friendly cellulose-based films.

Glucan polysaccharides isolated from Lactarius hatsudake Tanaka mushroom: Structural characterization and in vitro bioactivities.

Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with ß-(1,3)-Glcp as the main chain and ß-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Recombinant Klotho protein protects pulmonary alveolar epithelial cells against sepsis-induced apoptosis by inhibiting the Bcl-2/Bax/caspase-3 pathway.

BACKGROUND: Inflammation-induced apoptosis of alveolar type II epithelial cells is a primary contributor to sepsis-induced acute respiratory distress syndrome (ARDS). Klotho is a single-pass transmembrane protein with anti-inflammatory and anti-apoptotic effects. However, the role and mechanism of Klotho in the development of ARDS remains unknown. OBJECTIVES: This study aimed to investigate the effect of Klotho on sepsis-induced apoptosis in human pulmonary alveolar epithelial cells (HPAEpiCs) together with the potential mechanism. MATERIAL AND METHODS: Cecal ligation and puncture (CLP) were performed to generate an in vivo sepsis model, and HPAEpiCs were treated with lipopolysaccharide (LPS) to mimic sepsis in vitro. Both models were administered recombinant Klotho protein. The morphology of the lung tissue was observed, and apoptotic cells and cell viability were detected. Interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA), while the expression of Bcl-2, Bax and cleaved caspase-3 was detected with western blotting. RESULTS: Klotho reversed the CLP-induced decrease in mouse survival in vivo (p < 0.001) and increased inflammatory cell infiltration and inflammatory substance exudation in the lung tissue of mice with sepsis (both p < 0.001). Klotho also suppressed apoptosis (p < 0.001) as demonstrated by IL-1ß, IL-6 and TNF-α expression (all p < 0.001), and Bcl-2/Bax/caspase-3 pathway activation (p < 0.001). Klotho pretreatment significantly prevented LPS-induced apoptosis in vitro (p < 0.001), as demonstrated by IL-1ß, IL-6 and TNF-α upregulation (all p < 0.001); and Bcl-2/Bax/caspase-3 pathway activation in HPAEpiCs (p < 0.001). CONCLUSIONS: This study demonstrated that Klotho can ameliorate acute lung injury (ALI) induced by sepsis by inhibiting inflammatory responses and exerting anti-apoptotic effects by suppressing Bcl-2/Bax/caspase-3 pathway activation.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.