Safety and efficacy of irinotecan, oxaliplatin, and capecitabine (XELOXIRI) regimen with or without targeted drugs in patients with metastatic colorectal cancer: a retrospective cohort study.

BACKGROUND: Five-fluorouracil, folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) regimen is used as the first-line treatment for metastatic colorectal cancer (mCRC). The use of capecitabine, an oral fluoropyrimidine pro-drug, is feasible and safe; hence, it provides an interesting alternative to 5-fluorouracil in the abovementioned regimen. This study aimed to evaluate the efficacy and safety of capecitabine, oxaliplatin, and irinotecan (XELOXIRI) regimen use with or without targeted drugs in Chinese patients with mCRC. METHODS: We conducted a retrospective, longitudinal cohort study of patients with mCRC who received XELOXIRI regimen with or without targeted drugs (bevacizumab or cetuximab) every 2 weeks between January 2017 and November 2019 at the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment efficacy was assessed by investigators by evaluating the objective response rate (ORR) and disease control rate (DCR). Overall survival (OS) was assessed using Cox proportional hazards models. The adverse events were also analyzed. RESULTS: Sixty-one consecutive patients were examined and followed up for survival. As of November 8, 2021, the median follow-up time was 35.4 months. Disease progression and death occurred in 50 (82%) and 38 (62%) patients, respectively. The median treatment duration of XELOXIRI with or without bevacizumab or cetuximab was 10 cycles (range, 1-12 cycles). The median OS and PFS were 32.2 months (95%CI [24.8-39.6]) and 9.3 months (95% CI [8.1-10.5]), respectively. The ORR of 48 patients with measurable lesions was 70.8%, and the DCR was 89.6%. RAS/BRAF wild-type (HR 0.39; 95% CI [0.16-0.96], p = 0.04) and metastatic organs > 2 (HR 3.25; 95% CI [1.34-7.87], p = 0.009) were independent prognostic factors for OS. The incidence of any grade of adverse events (AEs) was 96.7% (59/61). Grade ≥ 3 AEs included neutropenia (19.7%), leukopenia (9.8%), diarrhea (3.3%), vomiting (3.3%), febrile neutropenia (1.6%), and thrombocytopenia (1.6%). No treatment-related death occurred. CONCLUSION: The use of the XELOXIRI regimen with or without a targeted drug was effective, with a manageable toxicity profile in Chinese patients with mCRC.

Construction of Highly Active Zn3In2S6 (110)/g-C3N4 System by Low Temperature Solvothermal for Efficient Degradation of Tetracycline under Visible Light.

Herein, Zn3In2S6 photocatalyst with (110) exposed facet was prepared by low temperature solvothermal method. On this basis, a highly efficient binary Zn3In2S6/g-C3N4 was obtained by low temperature solvothermal method and applied to the degradation of tetracycline (TC). The samples of the preparation were characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope, UV-vis diffuse reflection spectroscopy, and photoluminescence spectroscopy. Furthermore, the degradation performance of photocatalysts on TC was investigated under different experimental conditions. Finally, the mechanism of Zn3In2S6/g-C3N4 composite material degrading TC is discussed. The results show that Zn3In2S6 and Zn3In2S6/g-C3N4 photocatalysts with excellent performance could be successfully prepared at lower temperature. The Zn3In2S6/g-C3N4 heterojunction photocatalyst could significantly improve the photocatalytic activity compared with g-C3N4. After 150 min of illumination, the efficiency of 80%Zn3In2S6/g-C3N4 to degrade TC was 1.35 times that of g-C3N4. The improvement of photocatalytic activity was due to the formation of Zn3In2S6/g-C3N4 heterojunction, which promoted the transfer of photogenerated electron-holes. The cycle experiment test confirmed that Zn3In2S6/g-C3N4 composite material had excellent stability. The free radical capture experiment showed that ·O2- was the primary active material. This study provides a new strategy for the preparation of photocatalysts with excellent performance at low temperature.

Fabrication of ternary AgBr/BiPO4/g-C3N4 heterostructure with dual Z-scheme and its visible light photocatalytic activity for Reactive Blue 19.

A plasmonic photocatalyst of AgBr/BiPO4/g-C3N4 was prepared. X-ray powder diffraction, Scanning electron microscope, Transmission electron microscopy, Fourier infrared spectroscopy, Ultraviolet Visible diffuse reflectance spectroscopy and photoluminescence emission spectra have been employed to determine the structure, morphology and optical property of the as-prepared AgBr/BiPO4/g-C3N4 composite and analysis the reasons for improving photocatalytic efficiency. The optimal doping ratio of AgBr was 10 wt% by degrading 20 mg/L of Reactive Blue 19 (RB19) under visible light (λ > 420 nm), and 10 wt%AgBr/BiPO4/g-C3N4 degraded 20 mg/L of RB19 to 2.59% at 40 min, which is ascribed to synergistic effects at the interface of AgBr, BiPO4 and g-C3N4. The effect of catalyst dosage, initial concentration and initial pH of RB19 solution on photocatalytic efficiency was investigated. Four cycles of experiments were conducted. Finally, through the trapping experiment, we found that the main active factor for degrading RB19 in the photocatalytic process is O2-. The possible photocatalytic mechanism of AgBr/BiPO4/g-C3N4 was discussed in connection with the synergistic effect of Ag and active substances at the AgBr/BiPO4/g-C3N4 interface.

Atomic Force Microscopy Based Tip-Enhanced Raman Spectroscopy in Biology.

Most biological phenomena occur at the nanometer scale, which is not accessible by the conventional optical techniques because of the optical diffraction limitation. Tip-enhanced Raman spectroscopy (TERS), one of the burgeoning probing techniques, not only can provide the topography characterization with high resolution, but also can deliver the chemical or molecular information of a sample beyond the optical diffraction limitation. Therefore, it has been widely used in various structural analyses pertaining to materials science, tissue engineering, biological processes and so on. Based on the different feedback mechanisms, TERS can be classified into three types: atomic force microscopy based TERS system (AFM-TERS), scanning tunneling microscopy based TERS system (STM-TERS) and shear force microscopy based TERS system (SFM-TERS). Among them, AFM-TERS is the most widely adopted feedback system by live biosamples because it can work in liquid and this allows the investigation of biological molecules under native conditions. In this review, we mainly focus on the applications of AFM-TERS in three biological systems: nucleic acids, proteins and pathogens. From the TERS characterization to the data analysis, this review demonstrates that AFM-TERS has great potential applications to visually characterizing the biomolecular structure and crucially detecting more nano-chemical information of biological systems.

Hyperthermic intraperitoneal chemotherapy plus high-frequency diathermic therapy followed by intravenous chemotherapy versus intravenous chemotherapy alone for postoperative adjuvant treatment of gastrointestinal cancer: a comparative research study.

PURPOSE: To evaluate the therapeutic efficacy and toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) plus high-frequency diathermic therapy (HFDT) followed by intravenous chemotherapy vs intravenous chemotherapy alone for adjuvant treatment of postoperative gastrointestinal neoplasms. METHODS: Fifty-two gastrointestinal carcinoma patients who were radically operated were enrolled and divided into the treatment group and the control group. In the treatment group, 25 patients were treated with combination of HIPEC+HFDT and subsequent intravenous chemotherapy, while in the control group 27 patients received intravenous chemotherapy alone. Post-therapeutic complications and adverse reactions, time to progression (TTP) and overall survival (OS) were compared between these two groups. RESULTS: Difference in toxic reactions between the two groups was not statistically significant (p>0.05). Postoperative progression- free survival (PFS) rate at 12 and 40 months after radical surgery was 72.0 and 54.0% respectively in the treatment group, and 65.8 and 11.5% respectively in the control group (p=0.108). TTP was statistically significantly longer in the treatment group than in the control group (median TTP 40.1 vs 18.5 months, p=0.027). Postoperative OS at 12 and 20 months after radical surgery was 88.0 and 78.0% respectively in the treatment group and 92.6 and 72.7% in the control group, without significant difference. CONCLUSION: After radical surgery, combination of HIPEC+HFDT and subsequent intravenous chemotherapy brings about superior PFS compared with intravenous adjuvant chemotherapy alone, while having no more complications and adverse reactions.

sCLU regulates cisplatin chemosensitivity of lung cancer cells in vivo.

BACKGROUND: In a previous analysis using a lung cancer cell line model, we have found that therapies directed against secreted clusterin (sCLU) and its downstream signaling targets pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed against sCLU on the DDP-based chemotherapy in vivo and explored the mechanism. METHODS: Using lung cancer cell lines, A549 cells and DDP-resistant A549 cells (A549(DDP)), we determined the effect of sCLU silencing using short interfering double-stranded RNA (siRNA) on chemosensitivity in immunocompromised mice bearing A549(DDP) tumors. We then determined the effect of sCLU overexpression via stable sCLU transfection on chemosensitivity in immunocompromised mice bearing A549 tumors. The effect of sCLU silencing or overexpression on pAkt and pERK1/2 expression and chemosensitivity in vivo was detected by Western blot assay. RESULTS: The results showed sCLU silencing increased the chemosensitivity of A549(DDP) cells to DDP in vivo via downregulation of pAkt and pERK1/2 expression. And sCLU overexpression decreased the chemosensitivity of A549 cells to DDP in vivo via upregulation of pAkt and pERK1/2 expression. CONCLUSIONS: We therefore concluded that the DDP-induced sCLU activation, which involved induction of pAkt and pERK1/2 activation that confer DDP resistance in immunocompromised mice and alteration of this balance, allows sensitization to the antitumor activity of cisplatin chemotherapy.

[The New Bacteria Expressing Recombinant Multi-epitope Vaccine against Helicobacter pylori and Its Microbiological Characteristics].

OJECTIVE: To construct the engineering bacteria with recombinant plasmid expressing the multi-epitope vaccine which composed of Helicobacter pylori urea membrane channel protein (UreI), Helicobacter pylori urease B subunit (UreB) and cholera toxin B subunit (CTB), and then to study it's microbiological characteristics. METHODS: The sequence contains some dominant epitopes of Helicobacter pylori UreI and UreB was designed, and ctB was added at the N-terminal, all the sequence were linked by flexible linkers. Codon optimization was done according to Escherichia coli (E. coli) BL21 (DE3) bias, the optimized sequence was designated BIB. BIB sequence was synthesized and cloned into plasmid pET28a(+). The recombinant plasmid was confirmed by restriction enzyme digestion and DNA sequencing. The recombinant protein BIB was expressed in E. coli BL21 (DE3) and analyzed by Western blot. RESULTS: The plasmid of pET28a(+)/BIB was constructed successfully, confirmed by restriction enzyme digestion and DNA sequencing. The recombinant protein BIB with relative molecular mass about 33 x 10(3) could be produced by E. coli BL21 (DE3) and was detected by Western blot. The relative molecular mass and N-terminal amino acid sequence of BIB were 100% identity with the design. CONCLUTION: The engineering bacteria with recombinant plasmid expressing the multi-epitope vaccine against Helicobacter pylori was constructed successfully. The recombinant protein BIB can be identified by anti-Sydney strain 1 of Helicobacter pylori (H. pylori SS1) polyclonal antibody and anti-CTB monoclonal antibody, which demonstrated that BIB has the expected antigenicity.

Numerical simulation of local and upwind temperature stratification on flow and dispersion in a bi-dimensional street canyon.

The thermal effect mainly includes boundary temperature stratification and the local thermal effect. The combined effect of these factors on flow and dispersion in a bi-dimensional canyon was investigated by the RANS and LES methods to evaluate their performance. The results, including the flow field, turbulent kinetic energy, temperature, heat flux, pollutant concentration and fluxes, were compared with the data from wind tunnel experiments. The comparison results showed that the RANS method severely overestimated the impact of windward heating on the flow in the canyon because of the lack of simulated flow separation ability and the limitation of the Boussinesq model, leading to an incorrect flow field and an incorrect temperature and concentration. In contrast, LES performed better mainly because of its ability to simulate flow separation. LES regenerated the right vortexes, flow field and low wind velocity. LES slightly overestimates the overall temperature in the canyon because heat exchange is eliminated in LES but difficult to avoid in the experiment. The difference in the air exchange rate at the roof level between the LES and wind tunnel data was no more than 5%, and the pollutant concentration distribution of the LES was almost the same as that of the experiments. This work emphasizes that the RANS method has limited ability to simulate flow and dispersion when the thermal effect is considered even at a reduced-scale, while LES can simulate the combined effects of incoming flow temperature stratification and local thermal effects. It is therefore suggested that if computing resources are limited and the temperature difference is not large, a steady-state calculation RANS can be used. Otherwise, LES must be performed.

Significant effect of posterior line treatment of HER2 positive advanced gastric cancer: A case report.

At present, there are few options for third line and above treatment of advanced gastric cancer and the single drug effect is poor. HER2 positive gastric cancer is an important subtype of gastric cancer and has certain immune characteristics. The combination of HER2 inhibitor and PD-1 inhibitor has a synergistic effect, and anti-tumor drugs targeting HER2 can play an anti-angiogenesis role by downregulating VEGF. We report a patient with HER2-positive gastric cancer who developed post-operative tumor recurrence and metastasis after adjuvant chemotherapy and radiotherapy. Trastuzumab combined with albumin paclitaxel was used as second-line treatment with progression-free survival for 9 months. In third line treatment, we retained trastuzumab and combined it with camrelizumab and apatinib. During the treatment period, although the patient stopped taking the drugs due to the side effects of camrelizumab and apatinib, he achieved a PFS of 10.4 months. Considering the good effect of the third line treatment, we added another PD-1 inhibitor and continued to combine trastuzumab treatment. We found that the patient still benefited from the treatment and continued to survive for another 4 months. At present, the patient is treated with DisitamabVedotin (HER2-ADC) combined with PD-1 inhibitor, and no overall survival outcome has been observed.

Numerical simulation of airflow and dispersion in 3D street canyons: the effect of atmospheric temperature stratification.

Based on the Reynolds-averaged Navier-Stokes (RANS) method, a modified standard k-ϵ turbulence model with a source term rooted on Monin-Obukhov similarity theory was used to investigate the effects of temperature stratifications on the flow field and pollutant dispersion in 3D street canyons. The results showed that airflow and pollutant transport was highly dependent on temperature stratifications. The vortex velocity in the canyon varied with temperature stratifications. With the more unstable conditions, the centre of the vortex was closer to the ground, and the intensity and turbulent kinetic energy of the eddy increased. Because the source of pollution was located on the ground, the pollutants migrated to the leeward side of the building with the eddy and then moved upstream or downstream with the airflow. Under neutral conditions, the pollutants migrated to the leeward side first with the eddy in the canyon and then mainly migrated downstream with the airflow but rarely migrated to the upstream street canyons. However, under unstable conditions, the pollutant concentration in the upstream street canyons also increased, mainly because the intensity of the vortex increased, which made the pollutant easier to transport upstream. According to the results of the pollutant flux analysis, the turbulent fluxes on the top plane of the buildings were positive and increased significantly with the more unstable conditions, indicating that turbulent fluxes play a positive leading role in the dispersion of pollutants. The transverse transport of the pollutants was mainly dominated by convective motion, and turbulent transport was relatively minor.

Advanced pancreatic cancer with KRAS wild-type and EGFR-sensitive mutation respond favorably to furmonertinib: A case report.

Pancreatic cancer is the leading cause of cancer death, and treatment options are limited and mostly ineffective. The patient we report had an EGFR exon 19 deletion and had disease progression in the short term after receiving three front-line treatment regimens. We administered furmonertinib and observed tumor shrinkage, decreased CA19-9. The progression-free survival (PFS) of furmonertinib was 4.7 months, and no adverse effects were observed. However, the patient did not benefit from subsequent nimotuzumab-based therapy. Targeted therapy driven by the detection of genetic signatures in this patient shows potential clinical benefit in refractory advanced pancreatic cancer.

Real-World Results of Raltitrexed Combined with S-1 and Bevacizumab in Heavily Pretreated Metastatic Colorectal Cancer.

Purpose: Treatment options for refractory metastatic colorectal cancer (CRC) are scarce. This retrospective study aimed to evaluate the efficacy and safety of raltitrexed combined with S-1 and bevacizumab in patients with heavily pretreated metastatic CRC in a clinical real-world setting. Patients and Methods: Records of patients with metastatic CRC refractory to standard therapies who initiated raltitrexed plus S-1 and bevacizumab from October 2017 to December 2021 were retrospectively reviewed at our institution. The study endpoints included median overall survival (OS), overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs). Results: Forty-four patients with metastatic CRC, who had previously undergone standard chemotherapy received the regimen comprising raltitrexed plus S-1 and bevacizumab. As of March 2022, the median follow-up was 23.2 months (95% confidence interval 15.8-30.6). The median OS and median PFS were 13.5 (95% CI 9.9-17.1) and 4.7 months (95% CI 3.6-5.8), respectively, with a 16-week PFS rate of 60.9%. Among 43 patients with measurable lesions, the ORR and DCR were 7.0% (3/43) and 65.1% (28/43), respectively. Patients without peritoneal metastases (P = 0.003, hazard ratio 0.160, 95% CI 0.048-0.531), lower carcinoembryonic antigen level (≤42.8 ng/mL) (P = 0.039, HR 0.382, 95% CI 0.153-0.952), and no previous treatment with both vascular endothelial growth factor inhibitors (VEGF) and S-1 (P = 0.020, HR 0.215, 95% CI 0.059-0.785) had better OS. The incidence of any grade of treatment-related AEs was 88.6%, most of which were mild to moderate, and no treatment-related deaths occurred. Conclusion: Raltitrexed combined with S-1 and bevacizumab shows promising antitumor activity and safety and could be an alternative for patients with metastatic CRC who are refractory or intolerant to standard therapy.

Real-Time Attitude Estimation for Spinning Projectiles by Magnetometer Based on an Adaptive Extended Kalman Filter.

The attitude measurement system based on geomagnetic information offers advantages such as small space requirements, fast response times, excellent resistance to high-overload conditions, and cost-effectiveness. However, during the flight process of a high-mobility guided spinning projectile, calculating attitude based on geomagnetic information often leads to non-unique solutions. To address this challenge, this paper proposes the Adaptive Extended Kalman Filter (AEKF) attitude estimation algorithm, based on geomagnetic vector information. Based on the analysis of the short-term attitude motion characteristics of the projectile, the Kalman state system equation and the nonlinear observation equation are established, along with real-time correction of the yaw angle and adaptive updates of parameters. The effectiveness of the algorithm is verified by simulations and experiments, demonstrating its ability to eliminate the dual solution problem inherent in traditional Single-Epoch algorithms. It notably improves the accuracy of pitch and roll angle estimation while providing precise estimates of attitude angular rates. Furthermore, the algorithm effectively mitigates the impact of magnetic disturbances on attitude determination. The proposed method has many potential applications in attitude measurement and navigation using geomagnetic data.

Autologous CIK cells combined with chemotherapy as the first-line treatment for locally advanced or metastatic gastric cancer is safe and feasible.

Aim: To evaluate the safety and initial efficacy of autologous cytokine-induced killer (CIK) cells combined with S-1+oxaliplatin (SOX) as the first-line treatment for locally advanced or metastatic gastric cancer (GC). Materials and methods: In this two-arm, single-center exploratory trial, patients with locally advanced or metastatic GC were randomly assigned (1:1) to receive autologous CIK cells in combination with SOX (CIK-SOX) or SOX alone. The primary endpoint was the incidence of adverse events (AEs). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) served as the secondary endpoints. Results: Fifty-nine patients were enrolled in the study between November 20, 2014 and September 6, 2017. A total of 31 patients received CIK-SOX and 28 patients received SOX. The most common AEs in both groups were gastrointestinal reaction, leucopenia, neutropenia, anemia, thrombocytopenia, hyperbilirubinemia, and elevated aspartate transaminase concentration, with a higher incidence of these conditions in the SOX group. The median PFS for the CIK-SOX and SOX groups was 6.9 and 4.9 months, respectively (hazard ratio (HR) 0.80, p=0.45). The respective median OS values were 17.8 and 9.75 months (HR 0.76, p=0.34). Patients who received more than three injections of specific lymphocyte subsets benefited the most from this combination therapy. Cox univariate and multivariate analyses showed that tumor metastasis to more than two organs was the main risk factor for PFS and OS. A total of 29 patients in the CIK-SOX group and 25 in the SOX group had measurable lesions. The ORR for the CIK-SOX and SOX groups was 55.2% and 32.0%, while the DCR was 93.1% and 88.0%, respectively. Conclusion: The safety of CIK-SOX as the first-line treatment for patients with locally advanced or metastatic GC was good. Although the PFS and OS in the CIK-SOX group were not statistically significantly different compared to the values in the SOX alone group, this treatment increased the PFS and OS duration, with the absolute improvement in OS of about 8.05 months. Continuous benefit from the CIK-SOX treatment was observed during long-term follow-up. Clinical trial registration: https://clinicaltrials.gov/study/NCT02504229?term=NCT02504229&rank=1, identifier ChiCTR-IPR-15005923; NCT02504229.

CDK12 Promotes the Proliferation, Migration, and Angiogenesis of Gastric Carcinoma via Activating the PI3K/AKT/mTOR Signaling Pathway.

Cyclin-dependent kinase 12 (CDK12) has been found to regulate tumor progression. However, its function in gastric carcinoma (GC) remains controversial. This work aimed to explore the exact effect of CDK12 on GC progression. We detected the expression of CDK12 in GC cells and normal gastric mucosal epithelial cells. Then CDK12 function on GC cell proliferation, migration, and angiogenesis was researched by colony formation experiment, Transwell experiment, and angiogenesis assay. Moreover, CDK12 effect on the PI3K/AKT/mTOR pathway activity was explored by western blot. Further, we used LY294002 (10 µM) to treat GC cells to verify whether CDK12 regulates GC progression by activating the PI3K/AKT/mTOR pathway. Additionally, CDK12 effect on the expression of prognostic factors of GC was detected by western blot, including alkaline phosphatase (ALP) and Ki67. Quantitative real-time polymerase chain reaction and western blot were utilized to evaluate the expression of mRNAs and proteins. As a result, CDK12 was upregulated in GC cells. CDK12 overexpression facilitated the proliferation, migration, and angiogenesis of GC cells. However, CDK12 silencing showed an opposite result. CDK12 overexpression activated the PI3K/AKT/mTOR pathway, but CDK12 silencing inactivated it in GC cells. The blockage of the PI3K/AKT/mTOR pathway induced by LY294002 treatment counteracted the promotion of CDK12 on the proliferation, migration, and angiogenesis of GC. Further, CDK12 silencing suppressed the expression of ALP and Ki67 proteins in GC cells. Taken together, CDK12 promotes the proliferation, migration, and angiogenesis of GC by activating the PI3K/AKT/mTOR pathway. It may be a novel target for GC treatment.

Inflammatory biomarkers in assessing severity and prognosis of immune checkpoint inhibitor-associated cardiotoxicity.

AIMS: Inflammatory biomarkers, including CRP, the neutrophil-to-lymphocyte ratio (NLR), and the neutrophil-to-eosinophil ratio (NER), may predict outcomes in cancer. However, their value in immune checkpoint inhibitor (ICI) therapy-associated cardiotoxicity remains elusive. We aimed to characterize the relationship of inflammatory markers with severity of ICI-related cardiotoxicities (iRCs) and prognosis among patients with iRCs. METHODS: Patients who were diagnosed with iRCs between January 2019 and December 2021 were retrospectively enrolled and were dichotomized based on iRC severity into low-grade (grade 1-2) vs. high-grade (grade 3-4) groups. RESULTS: Forty-seven patients were included. The median time-to-event from first ICI infusion to onset of iRCs was 35 days (IQR: 19.0-65.5 days). When compared with respective baseline values, cardiac biomarkers and inflammatory markers were significantly elevated at onset of iRCs. Compared with low-grade iRCs, NER at iRC onset was significantly increased among patients with high-grade iRCs (Group × Time, P < 0.01). When grouped by the median NER (184.33) at iRC onset, NER ≥ 184.33 was associated with high-grade iRCs (OR: 10.77, P < 0.05) and had a 36.3% increased mortality compared to the lower NER group (HR: 2.67, P < 0.05). CONCLUSIONS: In patients who develop iRCs, NER is significantly elevated at iRC onset, and higher NER correlates with greater iRC severity and higher mortality. Larger datasets are needed to validate these findings.

Lattice-dislocated Bi nanosheets for electrocatalytic reduction of carbon dioxide to formate over a wide potential window.

Electrochemical reduction of CO2 to HCOOH (ERC-HCOOH) is one of the most feasible and economically valuable ways to achieve carbon neutrality. Unfortunately, achieving optimal activity and selectivity for ERC-HCOOH remains a challenge. Herein, ultrathin Bi nanosheets (NS) with lattice dislocations (LD-Bi) were prepared by the topological transformation of Bi2O2CO3 NS under high current conditions. LD-Bi exhibited excellent activity and selectivity as well as stability in ERC-HCOOH. Electrochemical tests and DFT calculations revealed that the excellent performance of LD-Bi was attributed to lattice dislocations, which can induce the production of more active sites on the catalyst surface and improve the electronic transfer ability. In addition, LD-Bi was beneficial to enhance the adsorption of CO2 and key reaction intermediates (OCHO*), thus improving the reaction kinetics. The result provides a unique perspective on the crucial role of lattice dislocations, which may have a significant impact on highly selective electrochemical conversion of CO2.

Apatinib as maintenance therapy following standard first-line chemotherapy in extensive disease small cell lung cancer: A phase II single-arm trial.

BACKGROUND: There is a need for the development of therapies to delay cancer progression and prolong survival after initial chemotherapy for the treatment of small cell lung cancer (SCLC). Since apatinib has been found to exert promising effects on cancer patients after standard first-line chemotherapy, this study aimed to investigate apatinib as a maintenance treatment following first-line chemotherapy in extensive disease (ED)-SCLC. METHODS: The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib (250 mg/day) was administered during the chemotherapy interval and as maintenance therapy after 4-6 cycles until the patient's disease progressed, the patient died, or became intolerant to the drug's toxicity. RESULTS: The patients who received apatinib maintenance treatment had a median PFS of 3.7 months (95% CI: 1.3-6.2 months). The median OS was 16.3 months (95% CI: 9.7-22.8 months). The objective response rate and disease control rate were 50.0% and 66.7%, respectively. Two patients required dose reduction due to adverse effects (AEs). The most common AEs included hypertension (n = 4, 33.3%) and hand-foot-skin reaction (n = 2, 16.7%). One patient developed diarrhea, while another patient developed hemoptysis. The most serious AE was intestinal obstruction. CONCLUSIONS: Apatinib maintenance therapy showed promising efficacy and safety to extend the OS/PFS of patients with ED-SCLC, thus making it a potent therapeutic option in future clinical practice. Given the small sample size of this study, further studies with large sample sizes are needed to validate the findings of the present study.

Human infection with a reassortment avian influenza A H3N8 virus: an epidemiological investigation study.

A four-year-old boy developed recurrent fever and severe pneumonia in April, 2022. High-throughput sequencing revealed a reassortant avian influenza A-H3N8 virus (A/Henan/ZMD-22-2/2022(H3N8) with avian-origin HA and NA genes. The six internal genes were acquired from Eurasian lineage H9N2 viruses. Molecular substitutions analysis revealed the haemagglutin retained avian-like receptor binding specificity but that PB2 genes possessed sequence changes (E627K) associated with increased virulence and transmissibility in mammalian animal models. The patient developed respiratory failure, liver, renal, coagulation dysfunction and sepsis. Endotracheal intubation and extracorporeal membrane oxygenation were administered. H3N8 RNA was detected from nasopharyngeal swab of a dog, anal swab of a cat, and environmental samples collected in the patient's house. The full-length HA sequences from the dog and cat were identical to the sequence from the patient. No influenza-like illness was developed and no H3N8 RNA was identified in family members. Serological testing revealed neutralizing antibody response against ZMD-22-2 virus in the patient and three family members. Our results suggest that a triple reassortant H3N8 caused severe human disease. There is some evidence of mammalian adaptation, possible via an intermediary mammalian species, but no evidence of person-to-person transmission. The potential threat from avian influenza viruses warrants continuous evaluation and mitigation.

Generating hydrogen gas from methane with carbon captured as pure spheroidal nanomaterials.

Energy production by using hydrogen gas as a feedstock is considered to be one of the keys to creating clean energy, with the proviso that the gas is generated in a sustainable way with no emissions. A simple, self-sustaining process generating hydrogen gas from methane using inexpensive stainless steel wire-mesh catalysts at elevated temperatures (800 °C) is reported. A theoretical analysis of the production of electricity by this process revealed peak chain energy efficiencies up to 21% (emission free) when using a percentage of the produced hydrogen (approximately 40% of purified yield) as the heat source. In addition, a practical method has been developed to purify the carbon byproduct, affording essentially pure highly graphitic spheroidal carbon for advanced materials applications.