Exosome-derived circUPF2 enhances resistance to targeted therapy by redeploying ferroptosis sensitivity in hepatocellular carcinoma.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, the effectiveness of sorafenib is greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in the cancer's malignant advancement. However, the significance of exosomal circular RNAs in the development of resistance to sorafenib in HCC remains uncertain. METHODS: Ultracentrifugation was utilized to isolate exosomes (Exo-SR) from the sorafenib-resistant HCC cells' culture medium. Transcriptome sequencing and differential expression gene analysis were used to identify the targets of Exo-SR action in HCC cells. To identify the targets of Exo-SR action in HCC cells, transcriptome sequencing and analysis of differential expression genes were employed. To evaluate the impact of exosomal circUPF2 on resistance to sorafenib in HCC, experiments involving gain-of-function and loss-of-function were conducted. RNA pull-down assays and mass spectrometry analysis were performed to identify the RNA-binding proteins interacting with circUPF2. RNA immunoprecipitation (RIP), RNA pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence in situ hybridization (FISH), and rescue assays were used to validate the interactions among circUPF2, IGF2BP2 and SLC7A11. Finally, a tumor xenograft assay was used to examine the biological functions and underlying mechanisms of Exo-SR and circUPF2 in vivo. RESULTS: A novel exosomal circRNA, circUPF2, was identified and revealed to be significantly enriched in Exo-SR. Exosomes with enriched circUPF2 enhanced sorafenib resistance by promoting SLC7A11 expression and suppressing ferroptosis in HCC cells. Mechanistically, circUPF2 acts as a framework to enhance the creation of the circUPF2-IGF2BP2-SLC7A11 ternary complex contributing to the stabilization of SLC7A11 mRNA. Consequently, exosomal circUPF2 promotes SLC7A11 expression and enhances the function of system Xc- in HCC cells, leading to decreased sensitivity to ferroptosis and resistance to sorafenib. CONCLUSIONS: The resistance to sorafenib in HCC is facilitated by the exosomal circUPF2, which promotes the formation of the circUPF2-IGF2BP2-SLC7A11 ternary complex and increases the stability of SLC7A11 mRNA. Focusing on exosomal circUPF2 could potentially be an innovative approach for HCC treatment.

Effectiveness of different intrusion modes of maxillary anterior teeth with mini-implants in clear aligner treatment: a three-dimensional finite element analysis.

BACKGROUND: The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. METHODS: Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. RESULTS: For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. CONCLUSIONS: The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.

Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.

OBJECTIVE: Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees. DESIGN, PATIENTS AND MEASUREMENTS: The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis. RESULTS: Both patients were middle-aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin-angiotensin-aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves' disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs-Polyphen-2, SIFT, Mutation Taster and LRT. CONCLUSIONS: We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.

Multi-functional device: manipulating linear and circular-polarization conversion in a terahertz chiral metamaterial.

We propose a terahertz chiral metamaterial as a multi-functional device to manipulate asymmetry transmission of linear polarized waves, linear-to-elliptical polarization conversion and circular dichroism in transmission mode while asymmetry reflection of circular polarized waves. For incidence of linear polarized waves, dual-band asymmetry transmission is shown around 0.42 THz and 1.04 THz where asymmetry transmission factors reach up to two peak values: ∼0.51 and ∼0.55, respectively. Intense linear-to-elliptical polarization conversion occurs at 0.81 THz and 0.97 THz, respectively. For incidence of circular polarized waves, a strong circular dichroism appears at 0.36 THz where circular dichroism parameter reaches to ∼0.64 and asymmetry reflection is displayed around 0.36 THz with the maximum of asymmetry reflection factors approaching to 0.55.

Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism with susceptibility to prostate cancer: an updated meta-analysis.

OBJECTIVE: This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). METHODS: We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger's test, with the robustness of the findings verified by sensitivity analysis. RESULTS: Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14-2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11-2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11-2.80; DI vs. II: OR= 1.44, 95% CI: 0.99-2.10; DD vs. II: OR= 2.12, 95% CI: 1.15-3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger's test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. CONCLUSION: ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.

Theoretical investigation of a controlled unidirectional reflectionlessness by applying external voltage in an electro-optical plasmonic waveguide system.

We theoretically investigate an controlled unidirectional reflectionlessness and near perfect absorption by applying external voltage in an electro-optical plasmonic waveguide system based on near-field coupling between two resonators. The system consists of two resonators side coupled to a metal-dielectric-metal plasmonic waveguide. Based on the numerical simulation, when external voltage is U = 7.4 V, the reflections for forward and backward directions are close to 0 and 0.82 at frequency 144.18 THz, while the reflections for forward and backward directions are close to 0.81 and 0 at frequency 150.86 THz when external voltage is U = 1.5 V. And the high absorption for forward (backward) direction is ∼0.97 (∼0.99) at frequency 144.18 THz (150.86 THz).

Highly-dispersive unidirectional reflectionless phenomenon based on high-order plasmon resonance in metamaterials.

In this work, we design a structure of metamaterials that consists of double sliver-ring resonators, in which highly-dispersive unidirectional reflectionlessness and absorption are achieved based on high-order plasmon resonance. Reflections of +z and -z directions at 461.34 THz (456.68 THz) are ∼0 (0.82) and ∼0.85 (0) when the distance d=222.9 nm (259.8 nm), respectively. High absorption of ∼0.97 and the quality factor of ∼435 can be obtained in the loss metal structure at room temperature. What's more, unidirectional reflectionlessness is investigated at low temperature.

Dual-band unidirectional reflectionlessness at exceptional points in a plasmonic waveguide system based on near-field coupling between two resonators.

Dual-band unidirectional reflectionlessness at exceptional points is investigated theoretically in a non-Hermitian plasmonic waveguide system, based on near-field coupling by using only two resonators. The system consists of a metal-insulator-metal waveguide end-coupled to two nanohole resonators. The reflectivity for the forward (backward) direction is ∼0 (∼0) at frequency 205.20 THz (194.56 THz), while for the backward (forward) direction it is ∼0.76 (∼0.78). Moreover, the quality factors of the dual-band unidirectional reflectionlessness for forward and backward directions can reach ∼132 and ∼137, respectively.

Unidirectional reflectionless phenomena in a non-Hermitian quantum system of quantum dots coupled to a plasmonic waveguide.

Unidirectional reflectionless phenomena are investigated theoretically in a non-Hermitian quantum system composed of several quantum dots and a plasmonic waveguide. By adjusting the phase shifts between quantum dots, single- and dual-band unidirectional reflectionlessnesses are realized at exceptional points based on two and three quantum dots coupled to a plasmonic waveguide, respectively. In addition, single- and dual-band unidirectional perfect absorptions with high quality factors are obtained at the vicinity of exceptional points.

Dual-band unidirectional reflectionless phenomena in an ultracompact non-Hermitian plasmonic waveguide system based on near-field coupling.

Dual-band unidirectional reflectionlessness and coherent perfect absorption (CPA) are demonstrated in a non-Hermitian plasmonic waveguide system based on near-field coupling between a single resonator and the resonant modes of two resonators showing an electromagnetically induced-transparency-like (EIT-like) effect. The non-Hermitian plasmonic system consists of three metal-insulator-metal (MIM) resonators coupled to a MIM plasmonic waveguide.

Unidirectional reflectionless propagation in a non-ideal parity-time metasurface based on far field coupling.

We propose a scheme to achieve a controllable unidirectional reflectionless propagation at exceptional point (EP) in a non-ideal parity-time metasurface consisting of two silver ring resonators. The unidirectional reflectionless propagation can be manipulated by simply adjusting the angle of incident wave and the distance s between two silver rings based on the far field coupling. In addition, the angle of incident wave in a wide range of ∼25° is available to achieve the unidirectional reflectionless propagation. Moreover, the unidirectional reflectionless propagation at EP is insensitive to the polarization of incident wave due to the two-ring structure.

[Dynamic changes of pH2AX expression in the reversibility of mouse testicular reproductive function impaired by single heat stress].

OBJECTIVE: To investigate the role of pH2AX in the reversibility of mouse testicular reproductive function impaired by single heat stress. METHODS: Twenty-four C57 male mice were randomly divided into heat stress and control groups and immersed in water at 43℃ and 25℃, respectively, for 15 minutes. At 1, 7, and 14 days of heat exposure, all the mice were sacrificed and their testis tissues collected for determining the apoptosis of the germ cells by TUNEL and measuring the expression level of the pH2AX protein by immunohistochemistry and Western blot. RESULTS: The highest percentage of apoptotic cells were found in the seminiferous tubules of the mice in the heat stress group on the 1st day of the exposure and almost no apoptosis was observed at 7 and 14 days. The pH2AX protein was expressed in the nuclei of the basement membrane of adjacent seminiferous tubules. Compared with the control group, the expression of pH2AX was significantly increased on the 1st day of exposure (0.47 ± 0.02 vs 1.61 ± 0.04, P <0.01), then decreased at 7 days (0.85 ± 0.03) in comparison with that on the 1st day (P <0.01), and again elevated at 14 days (1.72 ± 0.02) as compared with either those at 1 and 7 days (P <0.01) or that of the control (P <0.01). CONCLUSIONS: Heat stress causes dynamic changes of the pH2AX expression in the testis of the mouse, which are associated with heat stress-induced proliferation and division of the testicular spermatogenic cells.

[Quality of Schisandrae Chinensis Fructus regionalization based on GIS technology].

This paper is aims to clarify the spatial distribution of high quality medicinal materials Schisandrae Chinensis Fructus. Based on investigation and field investigation, the samples and distribution information of Schisandrae Chinensis Fructus were collected. Based on the data of four kinds of lignin chemical constituents, ecological environment factors and spatial distribution data of Schisandrae Chinensis Fructus, using GIS technology, maximum information entropy model and SPSS statistical analysis method for regionalizing the quality of Schisandrae Chinensis Fructus. The results showed that Schisandrae Chinensis Fructus was mainly distributed in the northeast of Liaoning, east of Jilin, east of Heilongjiang. The content of schisandrin was higher in the samples from northeastern part of Jilin province and the northeastern part of Liaoning province, The content of deoxyschizandrin was higher in the samples from middle of Jilin province and northeastern Hebei province, where the content of schisandrin B was higher in the samples from Jilin area, The higher schisantherin A sample were from southeast of Jilin and northeast of Liaoning. Considering the content of four components in Schisandrae Chinensis Fructus, the quality of Schisandrae Chinensis Fructus was concentrated in the southeast of Jilin and the northeastern part of Liaoning.

Amyand's hernia in a neonate: A case report.

Acute appendicitis secondary to hernia incarceration presenting as scrotal swelling is exceptionally rare in neonates. We report a neonate who presented with tender swelling in the right scrotum. Ultrasonography detected features of a rare Amyand's hernia. Surgical exploration and histopathological examination confirmed the diagnosis.

Radical nephrectomy for a giant chromophobe renal cell carcinoma diagnosed > 17 years previously: a case report and literature review.

Early diagnosis of renal cell carcinoma relies on imaging tests such as ultrasound, computed tomography, or magnetic resonance imaging. Since surgery is associated with a favorable prognosis, the standard treatment for clinically limited renal cell carcinoma remains surgical resection. Among asymptomatic patients with localized renal cell carcinoma, a small number refuse surgical treatment and survive. We report a case involving a 59-year-old female who underwent a difficult radical nephrectomy 17 years after being diagnosed with malignant tumors due to primary renal cell carcinoma.

Synergistic Effects of Shed-Derived Exosomes, Cu2+, and an Injectable Hyaluronic Acid Hydrogel on Antibacterial, Anti-inflammatory, and Osteogenic Activity for Periodontal Bone Regeneration.

The primary pathology of periodontitis involves the gradual deterioration of periodontal tissues resulting from the inflammatory reaction triggered by bacterial infection. In this study, a novel drug for periodontal pocket injection, known as the Shed-Cu-HA hydrogel, was developed by incorporating copper ions (Cu2+) and Shed-derived exosomes (Shed-exo) inside the hyaluronic acid (HA) hydrogel. Suitable concentrations of Cu2+ and Shed-exo released from Shed-Cu-HA enhanced cell viability and cell proliferation of human periodontal ligament stem cells. Additionally, the Shed-Cu-HA demonstrated remarkable antibacterial effects against the key periodontal pathogen (Aa) owing to the synergistic effect of Cu2+ and HA. Furthermore, the material effectively suppressed macrophage inflammatory response via the IL-6/JAK2/STAT3 pathway. Moreover, the Shed-Cu-HA, combining the inflammation-regulating properties of HA with the synergistic osteogenic activity of Shed-exo and Cu2+, effectively upregulated the expression of genes and proteins associated with osteogenic differentiation. The experimental findings from a mouse periodontitis model demonstrated that the administration of Shed-Cu-HA effectively reduced the extent of inflammatory cell infiltration and bacterial infections in gingival tissues and facilitated the regeneration of periodontal bone tissues and collagen after 2 and 4 weeks of injection. Consequently, it holds significant prospects for future applications in periodontitis treatment.

Effects of integrated nursing and psychological intervention on pain relief and patient satisfaction in urinary calculi patients.

OBJECTIVE: We aimed to assess the impact of integrated nursing and psychological intervention on pain intensity and patient satisfaction in individuals with urinary calculi. METHODS: This retrospective study included 94 urological patients from the Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, between January 2020 and June 2022. Participants were divided into a control group (n=48), receiving routine nursing and psychological intervention, and a study group (n=46), receiving integrated nursing and psychological intervention. We compared pain intensity, pain relief rate, patient satisfaction, Numeric Rating Scale (NRS) score, Pittsburgh Sleep Quality Index (PSQI) score, Self-rating Depression Scale (SDS) score, Self-rating Anxiety Scale (SAS) score, and quality of life scores between the groups. RESULTS: The study group had shorter hospital stays and lower hospitalization costs than the control group (both P < 0.05). Pain relief and satisfaction rates were higher in the study group (both P < 0.05). Post-intervention, both groups showed significant reductions in NRS, PSQI, SDS, and SAS scores, with greater reductions in the study group (all P < 0.05). Quality of life scores increased in both groups, more so in the SG (P < 0.05). The study group also had fewer adverse events (P < 0.05). Both groups showed decreased serum creatinine and blood urea nitrogen levels post-intervention, with a more significant decline in the study group (P < 0.05). Education, marital status, and occupation were major factors influencing outcomes in urinary calculi patients. CONCLUSION: Integrated nursing and psychological intervention significantly alleviates pain, improves emotional well-being, enhances sleep quality, increases overall life quality, and contributes to high patient satisfaction among urinary calculi patients.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria.

BACKGROUND: Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key. AIM: To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT. METHODS: Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4',6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively. RESULTS: Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 µmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria. CONCLUSION: Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

[Determination of eighteen elements in Serratulae Chinensis Radix by ICP-MS].

OBJECTIVE: To establish a method for the determination of eighteen elements (Be, Al, Cr, Mn, Ni, Cu, As, Se, Mo, Ag, Cd, Sn, Sb, Ba, Dy, Hg, Tl and Pb) in Serratulae Chinensis Radix by inductively coupled plasma-mass spectrography (ICP-MS). METHODS: After microwave digestion, 18 elements in the samples were determined by ICP-MS and the method was validated. RESULTS: A good linearity of calibration curves was obtained, the mean recovery met the analytical requirement. CONCLUSION: This method is simple, accurate and effective. It provides basis for the research of Serratulae Chinensis Radix.

LncRNA AATBC indicates development and facilitates cell growth and metastasis of cervical cancer as a sponge of miR-1245b-5p.

With the increasing incidence and mortality rate, cervical cancer has been considered one of the most frequent malignant tumors in females. Exploration of tumor progression-related biomarkers could facilitate the identification of novel and targeted therapy strategies. To assess the significance of lncRNA AATBC (AATBC) and its potential regulatory mechanism in cervical cancer, and to identify a potential biomarker, this study enrolled 123 patients with cervical cancer. Paired tissue samples were collected. The expression levels of AATBC and miR-1245b-5p were analyzed by RT-qPCR and their significance in the development and prognosis of cervical cancer was evaluated using chi-square and Cox analyses. In vitro, the regulatory effect of AATBC on the cellular processes of cervical cancer was estimated by CCK8 and Transwell assay. The interaction between ATTBC and miR-1245b-5p was assessed by luciferase reporter assay. Significant upregulation of AATBC and reduced miR-1245b-5p level in cervical cancer were observed, which showed a negative correlation between their expression levels. Close relationships of AATBC and miR-1245b-5p with the FIGO stage and lymph node metastasis were revealed. AATBC showed a significant prognostic value and miR-1245b-5p was found to mediate the tumor inhibitory effect of AATBC knockdown, which is speculated to be the underlying molecular mechanism of AATBC in cervical cancer development. Upregulation of AATBC indicted the malignant development and adverse prognosis of cervical cancer. AATBC served as a tumor promoter of cervical cancer by modulating miR-1245b-5p.