A novel role for WZ3146 in the inhibition of cell proliferation via ERK and AKT pathway in the rare EGFR G719X mutant cells.

Mutations in the epidermal growth factor receptor (EGFR) gene are common driver oncogenes in non-small cell lung cancer (NSCLC). Studies have shown that afatinib is beneficial for NSCLC patients with rare EGFR mutations. However, the effectiveness of tyrosine kinase inhibitors (TKIs) against the G719X (G719A, G719C and G719S) mutation has not been fully established. Herein, using the CRISPR method, the EGFR G719X mutant cell lines were constructed to assess the sensitivity of the rare mutation G719X in NSCLC. WZ3146, a novel mutation-selective EGFR inhibitor, was conducted transcriptome sequencing and in vitro experiments. The results showed that WZ3146 induced cytotoxic effects, inhibited growth vitality and proliferation via ERK and AKT pathway in the EGFR G719X mutant cells. Our findings suggest that WZ3146 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation G719X.

Effect of Personalized Nutrition Combined with Acceptance and Commitment Therapy on Psychological Resilience, Quality of Life and Side Effects of Chemotherapy in Patients with Advanced Gastric Cancer.

Aims/Background Gastric cancer is a common and life-threatening cancer, which predisposes patients to certain psychological problems. Implementation of both personalized nutrition and acceptance and commitment therapy (ACT) have shown unique advantages in the treatment of cancer patients. This study aims to evaluate the effects of this comprehensive therapy on psychological resilience, quality of life and side effects of chemotherapy in patients with advanced gastric cancer (AGC), yielding findings that can inform the development of holistic and effective treatment methods. Methods The clinical data of 240 AGC patients who underwent chemotherapy in the Fourth Hospital of Hebei Medical University from February 2021 to February 2023 were retrospectively analyzed. After excluding 15 patients who did not meet the inclusion criteria, 225 patients were included in the study. According to the management methods, the patients were divided into three groups: group A receiving routine management (n = 76), group B receiving routine management plus personalized nutrition (n = 75), and group C receiving routine management, personalized nutrition and ACT (n = 74). The psychological resilience, quality of life and side effects of chemotherapy were evaluated in the three groups. Results There was no difference in the Connor-Davidson resilience scale (CD-RISC) scores and quality of life questionnaire-core 30 (QLQ-C30) scores among the three groups at admission (p > 0.05). After chemotherapy, compared with the group C, the CD-RISC scores of group A and group B were significantly lower (p < 0.001), and the scores of physical function, cancer-related symptoms and overall health in group A and group B were significantly lower (p < 0.001). The incidence of side effects of chemotherapy in group C was 25.68%, which was significantly lower than that in group A and group B (p < 0.05); there was no statistical difference in this regard between group A and group B (p > 0.05), and the same parameter was significantly different between group A and group C (p < 0.05). Conclusion Personalized nutrition management plus ACT has a significant favorable effect on improving psychological resilience, alleviating the side effects of chemotherapy, and enhancing the quality of life in patients with AGC undergoing chemotherapy.

Suppressor tRNA in gene therapy.

Suppressor tRNAs are engineered or naturally occurring transfer RNA molecules that have shown promise in gene therapy for diseases caused by nonsense mutations, which result in premature termination codons (PTCs) in coding sequence, leading to truncated, often nonfunctional proteins. Suppressor tRNAs can recognize and pair with these PTCs, allowing the ribosome to continue translation and produce a full-length protein. This review introduces the mechanism and development of suppressor tRNAs, compares suppressor tRNAs with other readthrough therapies, discusses their potential for clinical therapy, limitations, and obstacles. We also summarize the applications of suppressor tRNAs in both in vitro and in vivo, offering new insights into the research and treatment of nonsense mutation diseases.

Almonertinib and alflutinib show novel inhibition on rare EGFR S768I mutant cells.

PURPOSE: EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified. METHODS: In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs. RESULTS: The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis. CONCLUSIONS: These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.

BDTX-189, a novel tyrosine kinase inhibitor, inhibits cell activity via ERK and AKT pathways in the EGFR C797S triple mutant cells.

The tertiary mutation C797S in the structural domain of the EGFR kinase is a common cause of resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs). In this study, we used a potent, selective and irreversible inhibitor, BDTX-189, to target EGFR C797S triple mutant cells for cell activity. The study constructed the H1975-C797S (EGFR L858R/T790 M/C797S) cell line using the CRISPR/Cas9 method and investigated its potential as a fourth-generation tyrosine kinase inhibitor via chemosensitivity approach. The results demonstrated its ability to induce cytotoxic effects, and inhibit EGFR L858R/T790 M/C797S cell growth and proliferation in a dose-dependent manner. Meanwhile, BDTX-189 reduces the protein phosphorylation levels of EGFR, ERK, and AKT, promoting apoptosis. Furthermore, BDTX-189 not only inhibits common EGFR triple mutations but also effectively inhibits EGFR L858R mutation and EGFR L858R/T790 M mutation. These findings support the cytotoxic effect of BDTX-189 and its inhibitory effect on cell division and proliferation with the EGFR C797S triple mutation.

Early diagnosis for the onset of peri-implantitis based on artificial neural network.

The aim of this study is to construct an artificial neural network (ANN) based on bioinformatic analysis to enable early diagnosis of peri-implantitis (PI). PI-related datasets were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and functional enrichment analyses were performed between PI and the control group. Furthermore, the infiltration of 22 immune cells in PI was analyzed using CIBERSORT. Hub genes were identified with random forest (RF) classification. The ANN model was then constructed for early diagnosis of PI. A total of 1,380 DEGs were identified. Enrichment analysis revealed the involvement of neutrophil-mediated immunity and the NF-kappa B signaling pathway in PI. Additionally, higher proportion of naive B cells, activated memory CD4 T cells, activated NK cells, M0 macrophages, M1 macrophages, and neutrophils were observed in the soft tissues surrounding PI. From the RF analysis, 13 hub genes (ST6GALNAC4, MTMR11, SKAP2, AKR1B1, PTGS2, CHP2, CPEB2, SYT17, GRIP1, IL10, RAB8B, ABHD5, and IGSF6) were selected. Subsequently, the ANN model for early diagnosis of PI was constructed with high performance. We identified 13 hub genes and developed an ANN model that accurately enables early diagnosis of PI.

Effect of Conventional Nursing Combined with Bedtime Oculomotor Training on Sleep Quality and Body Immunity of Advanced Lung Cancer Patients.

Objective: The aim of this study is to explore the effect of conventional nursing combined with bedtime oculomotor training on sleep quality and body immune of advanced lung cancer patients. Methods: By means of a retrospective study, 120 advanced lung cancer patients admitted to our hospital from January 2019 to January 2020 were selected as the research subject and divided into the intervention group (PSQI (Pittsburgh Sleep Quality Index) score≥10 points, n = 60) and the control group (PSQI score<10 points, n = 60). Conventional nursing was performed to the control group, and an eye movement exercise before sleep was added additionally in the intervention group, 30 min each time, once a day, and 5 times a week for 3 months, so as to compare their sleep quality, body immunity indexes, negative emotion scores, adverse reaction rate (ARR), quality of life, and satisfaction with nursing. Results: After nursing, the intervention group obtained a significantly lower PSQI score (5.54 ± 1.23 VS 7.98 ± 1.65, P < 0.05), better body immunity indexes (P < 0.001), lower negative emotion scores (P < 0.05), lower ARR (P < 0.05), better quality of life (P < 0.001), and higher satisfaction with nursing (P < 0.05) than the control group. Conclusion: Combining conventional nursing with the eye movement exercise before sleep can alleviate negative emotions, improve the sleep quality, promote body immunity, and reduce the ARR, which is more satisfying to patients and should be applied and promoted in practice.

Effect of Eye Movement Training on Sleep Quality of Patients with Advanced Lung Cancer Based on Pittsburgh Sleep Quality Index.

OBJECTIVE: To explore the effect of eye movement training on sleep quality of patients with advanced lung cancer based on the Pittsburgh Sleep Quality Index (PSQI). METHODS: 120 advanced lung cancer patients admitted to our hospital from January 2019 to January 2020 were selected as the research object and divided into group A (PSQI scores ≥ 10 points, n = 60) and group B (PSQI < 10 points, n = 60). Routine nursing was performed to both groups, and patients in group A received the eye movement training additionally, so as to compare their PSQI scores, negative emotion scores, adverse reaction rate (ARR), Cancer Coping Modes Questionnaire (CCMQ) scores, and pain scores. RESULTS: After training, group A obtained significantly better sleep quality (P < 0.05), lower negative emotion scores (P < 0.001), lower ARR (P < 0.05), better CCMQ scores (P < 0.05), and lower pain scores (P < 0.001) than group B. CONCLUSION: Eye movement training should be promoted in practice because it can reduce negative emotions, alleviate pain sensation, improve sleep quality and body condition, and lower the ARR for advanced lung cancer patients.

Effect of Narrative Nursing Intervention Based on Targeted Nursing Intervention on Anxiety and Nursing Satisfaction of Patients with Malignant Tumors Undergoing Chemotherapy.

Objective: To explore the effect of narrative nursing intervention based on targeted nursing intervention on anxiety and nursing satisfaction of patients with malignant tumors undergoing chemotherapy. Methods: 120 malignant tumor patients treated with chemotherapy in our hospital from January 2019 to January 2020 were selected as the research objects and randomly divided into group A and group B, with 60 cases in each group. The targeted nursing intervention was performed to group B, and the targeted nursing intervention centering on narrative nursing was performed to group A, so as to compare their distress thermometer (DT) scale scores, depression and anxiety scale scores, Medical Coping Modes Questionnaire (MCMQ) scores, Functional Assessment of Cancer Therapy-General (FACT-G) scores for quality of life, and nursing satisfaction. Results: After nursing intervention, group A obtained 5.00 ± 1.20 points in the DT score, which were significantly lower than group B (P < 0.05); and group A achieved significantly lower depression and anxiety scale scores (P < 0.001), better MCMQ scores (P < 0.05), and higher FACT-G scores (P < 0.05) and nursing satisfaction (P < 0.05) than group B. Conclusion: The targeted nursing intervention based primarily on narrative nursing can greatly reduce negative emotions, alleviate anxiety, and improve confidence in treatment and quality of life for malignant tumor patients undergoing chemotherapy, with higher nursing satisfaction, which should be promoted and applied in the practice.

Analysis of Nursing Effect and Impact of Narrative Nursing Model on Anxiety of Tumor Patients with PICC under Chemotherapy.

OBJECTIVE: To explore the nursing effect of the narrative nursing model on tumor patients with PICC under chemotherapy and the impact on patients' anxiety. METHODS: 200 tumor patients with PICC under chemotherapy treated in our hospital from March 2019 to March 2021 were randomly selected and divided into the control group (routine nursing) and the experimental group (narrative nursing) by the draw method, with 100 cases each. All patients were investigated with the General Anxiety Disorder-7 (GAD-7) scale, and their anxiety scores were over 5 points. The GAD-7 anxiety scores, satisfaction scores, Self-Rating Anxiety Scale (SAS) scores, Self-Rating Depression Scale (SDS) scores, quality of life (QLI) scores, and Mental Status Scale in Non-Psychiatric Settings (MSSNS) scores before intubation (T0), 1 d after intubation (T1), 3 d after intubation (T2), and after extubation (T3) of patients in both groups were compared. The adverse reaction rate (ARR) during placement was assessed in both groups, and the effectiveness of patient care was evaluated after extubation. RESULTS: Compared with the control group, the experimental group obtained significantly higher satisfaction scores and QLI scores at T0, T1, T2, and T3 and lower GAD-7 anxiety scores, SAS scores, SDS scores, and MSSNS scores at T0, T1, T2, and T3, which were statistically significant (P < 0.05). The experimental group had a significantly higher efficiency of care than the control group and a significantly lower ARR during treatment (P < 0.05). CONCLUSION: The narrative nursing model can remarkably improve the nursing effect, alleviate the anxiety, and provide a more quality nursing for tumor patients with PICC under chemotherapy.

The strategies to reduce cost and improve productivity in DHA production by Aurantiochytrium sp.: from biochemical to genetic respects.

The marine oleaginous protist Aurantiochytrium sp. (Schizochytrium sp.) is a well-known docosahexaenoic acid (DHA) producer and its different DHA products are the ideal substitute for the traditional fish oil resource. However, the cost of the DHA products derived from Aurantiochytrium sp. (Schizochytrium sp.) is still high, limiting their wide applications. In order to reduce the cost or improve the productivity of DHA from the microbial resource, many researches are focusing on exploring the renewable and low-cost materials as feedbacks, and/or the stimulators for biomass and DHA production. In addition, the genetic engineering is also being used in the Aurantiochytrium sp. (Schizochytrium sp.) system for further improvement. These break the bottleneck of the DHA production by Aurantiochytrium sp. (Schizochytrium sp.) in some degree. In this review, the strategies used currently to reduce cost and improve DHA productivity, mainly from the utilizations of low-cost materials and effective stimulators to the genetic engineering perspectives, are summarized, and the availabilities from the cost perspective are also evaluated. This review provides an overview about the strategies to revolve the production cost and yield of the DHA by Aurantiochytrium sp. (Schizochytrium sp.), a theoretical basis for genetic modification of Aurantiochytrium sp. (Schizochytrium sp.), and a practical basis for the development of DHA industry. KEY POINTS : • Utilizations of various low-cost materials for DHA production • Inducing the growth and DHA biosynthesis by the effective stimulators • Reducing cost and improving DHA productivity by genetic modification • The availability from cost perspective is evaluated.

Protein Engineering of a Pyridoxal-5'-Phosphate-Dependent l-Aspartate-α-Decarboxylase from Tribolium castaneum for ß-Alanine Production.

In the present study, a pyridoxal-5'-phosphate (PLP)-dependent L-aspartate-α-decarboxylase from Tribolium castaneum (TcPanD) was selected for protein engineering to efficiently produce ß-alanine. A mutant TcPanD-R98H/K305S with a 2.45-fold higher activity than the wide type was selected through error-prone PCR, site-saturation mutagenesis, and 96-well plate screening technologies. The characterization of purified enzyme TcPanD-R98H/K305S showed that the optimal cofactor PLP concentration, temperature, and pH were 0.04% (m/v), 50 °C, and 7.0, respectively. The 1mM of Na+, Ni2+, Co2+, K+, and Ca2+ stimulated the activity of TcPanD-R98H/K305S, while only 5 mM of Ni2+ and Na+ could increase its activity. The kinetic analysis indicated that TcPanD-R98H/K305S had a higher substrate affinity and enzymatic reaction rate than the wild enzyme. A total of 267 g/L substrate l-aspartic acid was consumed and 170.5 g/L of ß-alanine with a molar conversion of 95.5% was obtained under the optimal condition and 5-L reactor fermentation.

[Molecular structure and luminescent property of bis(2-(4-methyl-2-hydroxyphenyl)benzothiazolate) zinc].

Bis(2-(4-methyl-2-hydroxyphenyl)benzothiazolate) zinc(Zn(4-MeBTZ)2) was synthesized. Its molecular structure was confirmed by single-crystal x-ray diffraction. Single-crystal data are as follows: space group triclinic, P-1; a = 8.989 9(11) angstroms, b =12.161 7 (15) angstroms, c = 12.871 9 (16) angstroms, alpha = 63.492 (2) degrees, beta = 84.825 (2) degrees, gamma =71.187 (2) degrees. The steric hindrance provided by introduction methyl groups on phenoxide ring prohibited effectively the formation of pentacoordinate complex. There is distinct intermolecular pi-pi interaction between molecules. The dihedral angle between the phenol and benzothiazolate rings of Zn(4-MeBTZ)2 is 2.166 degrees. The HOMO energy, LUMO energy and optical gap are -5.84, -3.46 and 2.37 eV, respectively. The maximum wavelength peak of PL spectra located at 470 nm. The double-layer devices were employed using Zn(4-MeBTZ)2 as emitter and NPB as hole-transport material. The EL spectra split into two peaks located at 501 and 544 nm respectively. The broadened EL spectra were demonstrated to be originated from the exciplexes formed at the interface between NPB and Zn(4-MeBTZ)2.

[Mechanism of advanced glycation end-products in the inducement of apoptosis of human gingival fibroblast and related effect of puerarin in the process].

OBJECTIVE: To observe the effect of synthesized advanced glycation end-products (AGE) on reactive oxygen species formation and apoptosis of the cultured human gingival fibroblast and investigate the potential mechanisms of AGE in the modification of periodontal impairment. METHODS: AGE products with different concentrations [0, 50, 150 mg/L AGE-human serum albumin (AGE-HSA)] were incubated with human gingival fibroblast for 48 h, respestively. Flow cytometry was used to detect intracellular reactive oxygen species and cell apoptosis. The culture media with 50 mg/L AGE-HSA was exposed to 0.24 mmol/L puerarin for 48 h and then cell apoptosis was measured. RESULTS: The values of cellular apoptotic rate in 0, 50, 150 mg/L AGE-HSA groups were (1.60 ± 0.30)%, (29.43 ± 1.45)%, (49.20 ± 4.43)%, respectively. The differences between each AGE-HSA group and control were statistically significant (P < 0.05). AGE-HSA increased cell apoptosis in a dose-dependent manner (150 mg/L > 50 mg/L > 0 mg/L, P < 0.05). The cellular fluorescence intensity value was elevated as the concentration of AGE-HSA increased (P < 0.05). After incubation of human gingival fibroblast with AGE-HSA for 48 h, there was a significant decrease in apoptotic rate in puerarin group [(6.37 ± 3.02)%], compared with the control [(29.43 ± 1.45)%, P < 0.05]. CONCLUSIONS: AGE can stimulate apoptosis of human gingival fibroblast, which may be mediated by oxidative stress. Puerarin may protect periodontal tissues by inhibiting the apoptosis.

Structure, charge-transfer and luminescent properties bis(2-methyl-8-hydroxyquinoline) gallium chloride.

Bis(2-methyl-8-hydroxyquinoline) Gallium Chloride (GaMq2Cl) has been synthesized and characterized by X-ray crystallography. It is known from X-ray diffraction data on single crystals that the crystals of GaMq2Cl were monoclinic, space group C2/c, a = 28.701 A, b = 9.5405 A, c = 15.1434 A, Z = 8. Its thermal stability, electron structures and structural stability were investigated by TG analysis and quantum chemical calculations. The complex was a thermally stable material, with decomposition temperature being 348 degrees C. The electron-transfer property of GaMq2Cl is of advantage over hole-transfer property. Under UV excitation at 365 nm, the complex emits blue fluorescence with the maximum emission peak at 471 nm. Finally, blue-green light-emitting devices using this complex as the emissive layer were also fabricated and investigated, with emission wavelength at 502 nm. The results promote GaMq2Cl as a good candidate for luminescent material.

[Synthesis and luminescence properties of europium (III) complexes].

Three types of europium complexes were synthesized by introducing benzoylacetone as the first ligand and 1, 10-phenanthroline, triphenylphosphine oxide, 2,2'-bipyridyl as the second ligand, respectively. The properties of above materials were characterized by infrared absorption spectra, UV-Vis absorption spectra and fluorescence spectra. Then, it was discussed that the different second ligands of europium complexes can affect their luminescence properties, and their intramolecular energy transfer models had been set up. The results indicated that ligands and complexes have a strong absorption of UV light and the three types of europium complexes exhibit characteristic luminescence of europium ion when excited by UV light. In addition, it is suggested that the fluorescence yield of europium complexes mostly depend on both the energy difference between the second ligand and the Eu3+ ion and the energy difference between the second ligand and the first ligand.

[A new type of iridium (III) phenylpyrazole complexes: synthesis, photophysical characterization].

New heteroleptic iridium(III) complexes (ppz)2Ir(LX), which consist of two cyclometalated ligands ppz(1-phenylpyrazole) together with an ancillary ligand LX (LX= 2-(2'-hydroxylphenyl)benzothiazole (BTZ), 2-(3'-methyl-2'-hydroxylphenyl) benzothiazole (3-MeBTZ), 2-(4'-methyl-2'-hydroxylphenyl) benzothiazole (4-MeBTZ) and 2-(4'-Trifluoromethyl-2'hydroxylphenyl) benzothiazole (4-tfmBTZ)), were synthesized and characterized. The molecular structures and photophysical properties were characterized and analyzed comparatively. The results show that the four complexes have basically similar UV-Vis absorption spectra, fluorescence excitation and emission spectra. Their maximum emission peaks are located at 583-615 nm, and accompanied by a lower intensity emission band around 400 nm. The weak emissions around 400 nm are ascribed to the radi ation transition of single state excition from ancillary ligand BTZ perturbed by metallic ion, and light emission around long-wave-length to the radiation transition of 3MLCT of Ir(BTZ) fragment. While the triplet state 3 MLCT of Ir(ppz)2 fragment might be quenched at room temperature. For all complexes, the excitations with maximum efficiency are located at 250-310 nm, which indicates that main contributor to light emitting is ligand-centered absorption (1pi-pi*) of ppz and BTZ rather than 3MLCT transitions, and thus provides a striking evidence that there is intersystem crossing from 1pi-pi* state to 3MLCT state in these complexes. Compared with Ir(ppz)3, these complexes not only have stronger phosphorescence at room temperature but also their emission color can be tuned by modifying ancillary ligand.

[Characterization and photoluminescence properties of a blue-light-emitting material].

Tris (2-methyl-8-hydroxyquinoline) aluminum (AlMeq3) was synthesized and purified by vacuum sublimation. The structure of the complex was characterized by 1H NMR, FTIR spectra and elemental analysis techniques. AlMeq3 consists of three 2-methyl-8-hydroxyquinoline ligands and one aluminum atom. Its thermal stability was studied by TG and DSC analysis and the result shows that AlMeq3 is a thermally stable material, with decomposition and crystalline transition temperature being 357 and 158 degrees C, respectively. Energy band structure was investigated by UV-Vis absorption spectra and fluorescence emission spectra. Experimental results show that its UV absorption bands were at about 246 and 390 nm, and the absorption band at about 246 nm can be assigned to pi--pi* of phenyl ring. AlMeq2 displays 8-hydroxyquinoline-oriented photophysical properties. The optical gap of AlMeq3: was about 2.85 eV, as determined by intrinsic absorption band edge of the complex in ethanol solution. Under UV excitation at 365 nm, the complex in ethanol solution emitted intensive blue fluorescence with the maximum emission peak at 479 nm, while the effective energy-transfer from the ligand to the central AlP+ ion occurred in the complex. AlMeq3 with bright blue photoluminescence can be applied as luminescent material in OLEDs.