The Applicability of Polyetheretherketone and Titanium Mesh in Cranioplasty: A Retrospective Comparative Analysis.

OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.

In Situ Analysis of Interfacial Morphological and Chemical Evolution in All-Solid-State Lithium-Metal Batteries.

Visualizing lithium (Li) ions and understanding Li plating/stripping processes as well as evolution of solid electrolyte interface (SEI) are critical for optimizing all-solid-state Li metal batteries (ASSLMB). However, the buried solid-solid interfaces present a challenge for detection which preclude the employment of multiple analysis techniques. Herein, by employing complementary in situ characterizations, morphological/chemical evolution, Li plating/stripping dynamics and SEI dynamics were efficiently decoupled and Li ion behavior at interface between different solid-state electrolytes (SSE) was successfully detected. The innovative combining experiments of in situ atomic force microscopy and in situ X-ray photoelectron spectroscopy on Li metal anode revealed interfacial morphological/chemical evolution and decoupled Li plating/stripping process from SEI evolution. Though Li plating speed in Li10GeP2S12 (LGPS) was higher than Li3PS4 (LPS), speed of SSE decomposition was similar and ~85% interfacial SSE turned into SEI during plating and remained unchanged in stripping. To leverage strengths of different SSEs, an LPS-LGPS-LPS sandwich electrolyte was developed, demonstrating enhanced ionic conductivity and improved interfacial stability with less SSE decomposition (25%). Using in situ Kelvin Probe Force Microscopy, Li-ion behavior at interface between different SSEs was effectively visualized, uncovering distribution of Li ions at LGPS|LPS interface under different potentials.

A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy.

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.

On-chip integrated metasystem for spin-dependent multi-channel color holography.

On-chip integrated metasurface driven by in-plane guided waves is of great interests in various light-field manipulation applications such as colorful augmented reality and holographic display. However, it remains a challenge to design colorful multichannel holography by a single on-chip metasurface. Here we present metasurfaces integrated on top of a guided-wave photonic slab that achieves multi-channel colorful holographic light display. An end-to-end scheme is used to inverse design the metasurface for projecting off-chip preset multiple patterns. Particular examples are presented for customized patterns that were encoded into the metasurface with a single-cell meta-atom, working simultaneously at RGB color channels and for several different diffractive distances, with polarization dependence. Holographic images are generated at 18 independent channels with such a single-cell metasurface. The proposed design scheme is easy to implement, and the resulting device is viable for fabrication, promising plenty of applications in nanophotonics.

Minor Spliceosomal 65K/RNPC3 Interacts with ANKRD11 and Mediates HDAC3-Regulated Histone Deacetylation and Transcription.

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA- and other RNA-processing machineries in the nucleus. However, these established couplings are all major spliceosome-related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural-related defects. The 65K-ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle-uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin-binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11-KD are due to the decreased common chromatin-binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

A Tumor-Targeting Dual-Modal imaging probe for nitroreductase in vivo.

Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO2) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis.

A near-infrared fluorescent probe for imaging peroxynitrite levels in paw edema mice and drug evaluation.

A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO- in living cells, image ONOO- in paw edema mice and evaluate anti-inflammatory drugs.

Pyrazolone compounds could inhibit CES1 and ameliorates fat accumulation during adipocyte differentiation.

Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases.

[Risk Assessment of Antibiotics in Agricultural Environment].

Antibiotics are widely used in animal husbandry, planting, and aquaculture in agricultural industries. A large amount of the parent antibiotics used are released into the environment through discharge via feces and urine, posing potential risks to human health and ecosystems. It is thus very important to understand how antibiotics in the agricultural environment threaten the ecological environment and human health. Accordingly, risk assessment of antibiotics in the environment has become the research focus in recent years. The aim of this study was to review the risk assessment methods of antibiotics. The results showed that the ecological environment risk has mainly been assessed by the risk quotient (RQ). Predicted no-impact concentrations (PNECs) are an important indicator for ecological environment risk assessment, but a definite value is still controversial. The hazard quotient (HQ) is generally used to assess health risks. At present, it is necessary to clarify the selection of antibiotic exposure pathways and toxicological thresholds. However, neither of these two methods have currently considered either mixed pollution or the risk of antibiotic metabolites. Further analysis indicated that the ecological risks of antibiotics in the water environment and feces/manure/soil environment were widespread, which had an impact on both the soil and water environment. The types of antibiotics with high risk were different for various cultivated types. The factors including test species, testing conditions, calculation methods, and soil types all affected the detection of PNECs. Human health risk caused by dietary intake of antibiotics was minimal, but it cannot be ignored given the seafood consumption in coastal areas. Moreover, quinolones have both high ecological and human health risks in the agricultural environment. Based on the amount of antibiotics in agriculture and the residual concentration or toxicity of antibiotics in the related environment, this study proposed a priority-control list of antibiotics in the agricultural environment and summarized the main problems in the current antibiotic risk assessment. It will provide helpful support for the scientific optimization of antibiotic risk assessment and the effective control of antibiotics in agricultural environments.

Blocking Sigmar1 exacerbates methamphetamine-induced hypertension.

AIM: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension. METHODS AND RESULTS: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-ß/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells. CONCLUSION: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-ß/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.

Dual-Mechanism Peptide SR25 has Broad Antimicrobial Activity and Potential Application for Healing Bacteria-infected Diabetic Wounds.

The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.

Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

The use of longitudinal CT-based radiomics and clinicopathological features predicts the pathological complete response of metastasized axillary lymph nodes in breast cancer.

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.

Adrenomedullin improved endothelial dysfunction via receptor-Akt pathway in rats with obesity-related hypertension.

Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions.

Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes.

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.