Chelating Effect of Siderophore Desferrioxamine-B on Uranyl Biomineralization Mediated by Shewanella putrefaciens.

In contaminated water and soil, little is known about the role and mechanism of the biometabolic molecule siderophore desferrioxamine-B (DFO) in the biogeochemical cycle of uranium due to complicated coordination and reaction networks. Here, a joint experimental and quantum chemical investigation is carried out to probe the biomineralization of uranyl (UO22+, referred to as U(VI) hereafter) induced by Shewanella putrefaciens (abbreviated as S. putrefaciens) in the presence of DFO and Fe3+ ion. The results show that the production of mineralized solids {hydrogen-uranium mica [H2(UO2)2(PO4)2·8H2O]} via S. putrefaciens binding with UO22+ is inhibited by DFO, which can both chelate preferentially UO22+ to form a U(VI)-DFO complex in solution and seize it from U(VI)-biominerals upon solvation. However, with Fe3+ ion introduced, the strong specificity of DFO binding with Fe3+ causes re-emergence of biomineralization of UO22+ {bassetite [Fe(UO2)2(PO4)2·8(H2O)]} by S. putrefaciens, owing to competitive complexation between Fe3+ and UO22+ for DFO. As DFO possesses three hydroxamic functional groups, it forms hexadentate coordination with Fe3+ and UO22+ ions via these functional groups. The stability of the Fe3+-DFO complex is much higher than that of U(VI)-DFO, resulting in some DFO-released UO22+ to be remobilized by S. putrefaciens. Our finding not only adds to the understanding of the fate of toxic U(VI)-containing substances in the environment and biogeochemical cycles in the future but also suggests the promising potential of utilizing functionalized DFO ligands for uranium processing.

Exploring the problems and coping strategies of pharmacy internship in large general hospitals in China: from the perspective of preceptors.

OBJECTIVE: The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. METHODS: This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. RESULTS: Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs' perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. CONCLUSION: This study found that from the HPPs' perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.

Seven oral traditional Chinese medicine combined with chemotherapy for the treatment of non-small cell lung cancer: a network meta-analysis.

CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Realization of a photoswitchable anapole metasurface based on phase change material Ge2Sb2Te5.

The electromagnetic anapole mode originates from the phase cancellation interference between the far-field radiation of an oscillating electric dipole moment and toroidal dipole moment, which presents a radiation-free state of light while enhancing the near-field, and has potential applications in micro- and nanophotonics. The active control of the anapole is crucial for the design and realization of tunable photonic devices. In this paper, we realize dynamic tuning of an anapole metasurface and metasurface optical switching based on the phase change material G e 2 S b 2 T e 5 (GST). By utilizing the destructive interference of the electric dipole moment and ring dipole moment, we design the non-radiative anapole mode. At the same time, we introduce the phase change material GST to dynamically regulate the intensity and position of the far-field scattering, electric field, and transmission spectra, and to realize the transition from anapole mode to electric dipole mode. At the same time, the modulation of the transmission spectrum by the metasurface after the addition of GST film is achieved. A relative transmission modulation of 640.62% is achieved. Our study provides ideas for realizing effective active modulation of active micro- and nanophotonic devices, and promotes active modulation of active micro- and nanophotonic devices in lasers and filters and potential applications in dynamic near-field imaging.

Mutational inactivation of mTORC1 repressor gene DEPDC5 in human gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma and are initiated by activating mutations in the KIT or PDGFRA receptor tyrosine kinases. Chromosome 22q deletions are well-recognized frequent abnormalities in GISTs, occurring in ∼50% of GISTs. These deletions are thought to contribute to the pathogenesis of this disease via currently unidentified tumor suppressor mechanisms. Using whole exome sequencing, we report recurrent genomic inactivated DEPDC5 gene mutations in GISTs (16.4%, 9 of 55 patients). The demonstration of clonal DEPDC5 inactivation mutations in longitudinal specimens and in multiple metastases from individual patients suggests that these mutations have tumorigenic roles in GIST progression. DEPDC5 inactivation promotes GIST tumor growth in vitro and in nude mice. DEPDC5 reduces cell proliferation through the mTORC1-signaling pathway and subsequently induces cell-cycle arrest. Furthermore, DEPDC5 modulates the sensitivity of GIST to KIT inhibitors, and the combination therapy with mTOR inhibitor and KIT inhibitor may work better in GIST patients with DEPDC5 inactivation. These findings of recurrent genomic alterations, together with functional data, validate the DEPDC5 as a bona fide tumor suppressor contributing to GIST progression and a biologically relevant target of the frequent chromosome 22q deletions.

Fast Driving of a Particle in Two Dimensions without Final Excitation.

Controlling the motional state of a particle in a multidimensional space is key for fundamental science and quantum technologies. Applying a recently found two-dimensional invariant combined with linear invariants, we propose protocols to drive a particle in two dimensions so that the final harmonic trap is translated and rotated with respect to the initial one. These protocols realize a one-to-one mapping between initial and final eigenstates at some predetermined time and avoid any final excitations.

Oncogenic ERBB2 aberrations and KRAS mutations cooperate to promote pancreatic ductal adenocarcinoma progression.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with few therapeutic options, representing one of the great challenges in oncology. Activating KRAS mutation, occurring in >90% PDACs, is present in pancreatic intraepithelial neoplasia lesions, the precursor ductal lesions of PDAC, indicating additional genetic alterations contribute to the pathogenesis of PDAC. PDAC sequencing projects identify recurrent genomic ERBB2 alterations, mutations and amplifications, in 8.5% of PDAC patients, ranking as the top hit among the 100 receptor tyrosine kinases-encoding genes. Introduction of the ERBB2 mutations encoding protein variants S310F, S423R, R678Q, Q679L, E717D, L755S, V777L and V842I into human pancreatic epithelial cells causes oncogenic transformation, increasing ERBB2 signaling, anchorage-independent cell growth and tumor xenograft growth in nude mice, demonstrating that they are activating mutations. Interestingly, in many PDACs, mutations in ERBB2 and KRAS occur together. ERBB2 activating mutants facilitate KRAS-driven oncogenic properties. Introduction of ERBB2 mutations into KRAS-mutant PDAC cells activates ERBB2 signaling, promotes tumor growth and attenuates KRAS dependency. In contrast, a CRISPR-mediated knockout (KO) of ERBB2 in ERBB2-amplified PDAC cells inhibits ERBB2 signaling, colony formation, anchorage-independent growth and tumor xenograft formation. Finally, oncogenic ERBB2 aberrations can be abrogated by treatment with small-molecule inhibitors. ERBB2 and KRAS inhibition cooperate to suppress PDAC cell growth in vitro and to promote tumor regression in nude mice, providing a rationale for testing an anti-ERBB2 drug in combination with a KRAS inhibitor in ERBB2-mutant PDAC patients that are currently untreatable.

Spectrum of activity of dasatinib against mutant KIT kinases associated with drug-sensitive and drug-resistant gastrointestinal stromal tumors.

BACKGROUND: The majority of GISTs express mutationally activated KIT. Imatinib and sunitinib are approved KIT-inhibiting therapies. Their efficacy is usually hampered by the acquired multiple secondary drug-resistance KIT mutations. The most problematic resistance subset is GISTs with acquisition of secondary mutations in the KIT activation loop. Here, we establish the spectrum of activity of dasatinib against a comprehensive collection of clinically relevant KIT mutants associated with drug-sensitive and drug-resistant GIST. METHODS: The cellular and in vitro activities of tyrosine kinase inhibitors (TKIs) against mutant KIT were assessed using a panel of engineered and GIST-derived cell lines. The in vivo activities of dasatinib were determined using TKI-resistant xenograft models. RESULTS: In engineered and GIST-derived cell lines, dasatinib potently inhibited KIT with primary mutations in exon 11 or 9 and a range of secondary imatinib-resistant mutations in exons 13 and 14, encoding the ATP-binding pocket, and in exons 17 and 18, encoding the activation loop, with the exception of a substitution at codon T670. Our data show that dasatinib is more potent than imatinib or sunitinib at inhibiting the activity of drug-resistant KIT mutants. Dasatinib also induces regression in GIST-derived xenograft models containing these secondary mutations. A major determinant of the efficacy of dasatinib for the treatment of advanced GIST is the activity of this inhibitor against KIT mutants. CONCLUSION: Dasatinib shows efficacy in cancer models, inhibiting a wide range of oncogenic primary and drug-resistant KIT mutants. These results have implications for the further development of dasatinib precision therapy in GIST patients.

Noise Sensitivities for an Atom Shuttled by a Moving Optical Lattice via Shortcuts to Adiabaticity.

We find the noise sensitivities (i.e., the quadratic terms of the energy with respect to the perturbation of the noise) of a particle shuttled by an optical lattice that moves according to a shortcut-to-adiabaticity transport protocol. Noises affecting different optical lattice parameters, trap depth, position, and lattice periodicity, are considered. We find generic expressions of the sensitivities for arbitrary noise spectra but focus on the white-noise limit as a basic reference, and on Ornstein-Uhlenbeck noise to account for the effect of non-zero correlation times.

Toll-like receptor 5 agonist CBLB502 induces radioprotective effects in vitro.

CBLB502 derived from Salmonella flagellin is a novel agonist of Toll-like receptor 5 (TLR5). It has been shown that CBLB502 can exert high radioprotective efficacy on mice and primates from both GI and hematopoietic syndromes during whole-body irradiation with low toxicity and immunogenicity. However, no effective system has been used to investigate the protective effect of CBLB502 against irradiation and the related mechanism in vitro. In this study, we investigated the radioprotective properties of CBLB502 in HEK293-N-T cells constitutively expressing human TLR5 and NF-κB-dependent luciferase. HEK293-N-T cells were treated with different doses of CBLB502 prior to 60Co-γ ray irradiation. After irradiation, cell viability was real-time measured for 4 days by using the real-time cell analysis system. We found that CBLB502 was capable of efficiently maintaining the survival rate of irradiated HEK293-N-T cells. Then apoptotic cell death and cell cycle were detected by flow cytometry. The results showed that CBLB502 pre-treatment could reduce the apoptosis and promote the recovery of irradiated HEK293-N-T cells from G2-phase arrest in a dose-dependent manner. Our data indicated that CBLB502 has a direct radioprotective effect in vitro via anti-apoptosis and promotes cell cycle recovery. The method developed here could be an effective in vitro system to screen other TLR5-target radioprotectants like CBLB502.

[The Diagnostics of Detonation Flow External Field Based on Multispectral Absorption Spectroscopy Technology].

Compared with traditional sampling-based sensing method, absorption spectroscopy technology is well suitable for detonation flow diagnostics, since it can provide with us fast response, nonintrusive, sensitive solution for situ measurements of multiple flow-field parameters. The temperature and concentration test results are the average values along the laser path with traditional absorption spectroscopy technology, while the boundary of detonation flow external field is unknown and it changes all the time during the detonation engine works, traditional absorption spectroscopy technology is no longer suitable for detonation diagnostics. The trend of line strength with temperature varies with different absorption lines. By increasing the number of absorption lines in the test path, more information of the non-uniform flow field can be obtained. In this paper, based on multispectral absorption technology, the reconstructed model of detonation flow external field distribution was established according to the simulation results of space-time conservation element and solution element method, and a diagnostic method of detonation flow external field was given. The model deviation and calculation error of the least squares method adopted were studied by simulation, and the maximum concentration and temperature calculation error was 20.1% and 3.2%, respectively. Four absorption lines of H2O were chosen and detonation flow was scanned at the same time. The detonation external flow testing system was set up for the valveless gas-liquid continuous pulse detonation engine with the diameter of 80 mm. Through scanning H2O absorption lines with a high frequency of 10 kHz, the on-line detection of detonation external flow was realized by direct absorption method combined with time-division multiplexing technology, and the reconstruction of dynamic temperature distribution was realized as well for the first time, both verifying the feasibility of the test method. The test results show that both of the temperature and H2O concentration rose with the arrival of detonation wave. With the increase of the vertical distance between the detonation tube nozzle and the laser path, the time of temperature and concentration coming to the peak delayed, and the temperature variation trend tended to slow down. At 20 cm from detonation tube nozzle, the maximum temperature hit 1 329 K and the maximum H2O concentration of 0.19 occurred at 4 ms after ignition. The research can provide with us the support for expanding the detonation test field with absorption spectroscopy technology, and can also help to promote the detonation mechanism research and to enhance the level of detonation engine control technology.

A novel substitution -sensing for hydroquinone and catechol based on a poly(3-aminophenylboronic acid)/MWCNTs modified electrode.

A facile electrochemical sensor for hydroquinone (HQ) and catechol (CC) determination was successfully fabricated by the modification of poly(3-aminophenylboronic acid) (pAPBA) film and multi-walled carbon nanotubes (MWCNTs) on a glassy carbon electrode (pAPBA/MWCNTs/GCE). The prepared sensor was characterized by scanning electron microscope and electrochemical impedance spectroscopy. Under optimal conditions, differential pulse voltammetry was employed to quantify individual HQ and CC within the concentration range of 5.0 × 10(-7)-4.0 × 10(-5) mol L(-1) and 7.0 × 10(-6)-1.0 × 10(-4) mol L(-1), respectively. Based on the covalent binding between the boronic acid groups of pAPBA film and the cis-diol-containing molecule, a novel substitution-sensing strategy was proposed for the highly sensitive determination of CC. With the addition of CC into HQ solution, covalent interaction between CC and APBA occurred and the HQ was displaced by CC, resulting in a decrease of HQ oxidation peak current and the increase of the CC oxidation peak current. The summation of both current changes (Δ|IHQ| + Δ|ICC|) were combined for CC sensitive detection in a concentration range of 4.0 × 10(-8)-1.7 × 10(-5) mol L(-1) with a limit of detection of 4.3 × 10(-9) mol L(-1). The sensor was successfully applied to the determination of CC in spiked water samples.

[Preparation and in vitro evaluation of crosslinked polyvinyl alcohol microspheres for embolization].

OBJECTIVE: To develop and study the properties of crosslinked polyvinyl alcohol microspheres (PVA-Ms) for embolization. METHODS: The PVA-Ms were produced by emulsion chemical crosslinking method. Fourier transform infrared spectroscopy (FT-IR) was used to investigate the special functional groups of PVA-Ms; the morphology and particle size of PVA-Ms were determined by optical microscope; the ratio of water absorption and the swelling ratio were also investigated; the compressibility was examined by texture analyzer. A new device was designed to measure the pressure of PVA-Ms during their delivery through catheter for embolization. RESULTS: The crosslinking reaction of PVA and formaldehyde was proved by FT-IR. The PVA-Ms were round with smooth surface. The average diameter of lyophilized PVA-Ms was 574.2 µm with a range of 80-1 800 µm and of wet PVA-Ms was 602.2 µm with a range of 100-1 900 µm. The average ratio of water absorption was 175% and the swelling ratio was 48.6%. The PVA-Ms were mechanically stable with appropriate elasticity and delivered through the catheter without any difficulty, and the pressure was higher for larger size of microspheres to be delivered. CONCLUSION: PVA-Ms prepared in this study was supposed to be suitable for clinical embolization according to the physicochemical properties. The study provides a series of methods to evaluate the properties of microspheres systemically for embolization in vitro.

[Preparation and property study of doxorubicin loaded microspheres].

OBJECTIVE: To prepare doxorubicin-loaded polyvinylalcohol-acrylic acid (PVA-AA) microspheres and evaluate properties of this chemoembolic agent. METHODS: PVA-AA microspheres were synthesized by inverse suspension polymerization method and then verified by infrared spectroscopy. drug loading (DL) and entrapment efficiency (EE%) were measured after doxorubicinwas loaded on PVA-AA microspheres. Their morphology and elasticity were investigated by optical microscope, environmental scanning electron microscope and texture analyzer, respectively. T-cell apparatus was used to evaluate the in vitro release behavior of doxorubicin-loaded microspheres.The external carotid of the rabbit was chosen as an embolization site to evaluate the in vivo embolic property of the microspheres. RESULTS: PVA-AA microspheres, which were transparent spheres,turned into red spheres after doxorubicin loading. DL of the microspheres was (20.56 ± 0.69)g/L and (23.25 ± 0.27) g/L,and EE% was 82.22% ± 2.76% and 93.00% ± 1.06% within 20 min and 6 h, respectively. The in vitro release results showed a significantly delayed release of the drug for 10.32% ± 0.47% after 24 h. The Young's modulus was (178.30 ± 12.33) kPa and (213.29 ± 15.61) kPa for blank microspheres and doxorubicin-loaded microspheres, respectively. Both blank microspheres and doxorubicin-loaded microspheres exhibited good elasticity. In vivo embolization showed that 0.3 mL of microspheres could produce distal embolic efficiency. CONCLUSION: The doxorubicin-loaded microspheres are expected to be a promising new chemoembolic agent.

[Research on diagnosis of gas-liquid detonation exhaust based on double optical path absortion spectroscopy technique].

The effect detection of detonation exhaust can provide measurement data for exploring the formation mechanism of detonation, the promotion of detonation efficiency and the reduction of fuel waste. Based on tunable diode laser absorption spectroscopy technique combined with double optical path cross-correlation algorithm, the article raises the diagnosis method to realize the on-line testing of detonation exhaust velocity, temperature and H2O gas concentration. The double optical path testing system is designed and set up for the valveless pulse detonation engine with the diameter of 80 mm. By scanning H2O absorption lines of 1343nm with a high frequency of 50 kHz, the on-line detection of gas-liquid pulse detonation exhaust is realized. The results show that the optical testing system based on tunable diode laser absorption spectroscopy technique can capture the detailed characteristics of pulse detonation exhaust in the transient process of detonation. The duration of single detonation is 85 ms under laboratory conditions, among which supersonic injection time is 5.7 ms and subsonic injection time is 19.3 ms. The valveless pulse detonation engine used can work under frequency of 11 Hz. The velocity of detonation overflowing the detonation tube is 1,172 m x s(-1), the maximum temperature of detonation exhaust near the nozzle is 2 412 K. There is a transitory platform in the velocity curve as well as the temperature curve. H2O gas concentration changes between 0-7% during detonation under experimental conditions. The research can provide measurement data for the detonation process diagnosis and analysis, which is of significance to advance the detonation mechanism research and promote the research of pulse detonation engine control technology.

Analysis of factors influencing family farms' adoption of green prevention and control techniques on an integrative framework of the TPB and NAM.

The application of green prevention and control techniques (GCTs) is a vital measure for improving the quality of agricultural products and enhancing the safety of the ecological environment and agricultural production. However, realistically, limited by the small-scale, part-time and decentralized business model, the adoption of GCTs by family farms in China faces practical problems such as insufficient internal transformation force and ability, as well as low external supervision efficiency. To reveal the directions of promoting family farms' GCTs adoption behavior, we establish a comprehensive theoretical model through the application of a novel integrated approach combining two dominant psychological theories of behavior change: the Theory of Planned Behavior (TPB) and the Norm Activation Model (NAM). We apply this framework to targeted research of vegetable growers in Henan Province in China using survey data (sample n = 653) analyzed through structural equation modeling (SEM). The integrated TPB-NAM model provides insight into both internal motivation and external environmental conditions for farmers' predicted adoption of GCTs. First, internal motivation, value cognition and personal norms are all driving factors affecting the GCTs behavioral intention of vegetable family farms. When GCTs are driven by the dual motivations of "self-interest" (personal norms) and "others-interest" (value cognition), personal norms can be activated by two factors: awareness of consequences and responsibility attribution. Furthermore, social norms, capital endowment and government regulation are the pressure and obstacle factors affecting the GCTs application of vegetable family farms. Social norms can indirectly affect the application of GCTs by forming personal norms. In addition, there are differences between the influencing factors and mechanism of GCTs adoption behavior intention of family farms of different sizes. Based on this, we propose some specific policy suggestions from three aspects: enhance value cognition, improve environmental awareness and responsibility perception, fill in the shortcomings of capital endowment, and implement differentiated incentive and restraint policies.

Hospital pharmacists' mental health during home isolation in the post-pandemic era of COVID-19: influencing factors, coping strategies, and the mediating effect of resilience.

Objective: There is a notable research gap on the mental health challenges faced by hospital pharmacists in the post-pandemic era. Therefore, the present study aims to explore mental health status, influencing factors, coping strategies, and the mediating effect of resilience of home quarantine hospital pharmacists (HQHPs). Methods: An embedded mixed-method study was conducted in Zhengzhou, a megalopolis in central China, from 20 October to 3 November 2022. For the qualitative study, semi-structured interviews and focus group discussions were conducted among HQHPs to understand their mental health state，the factors that affect their mental health, and the alleviating strategies they used. For the quantitative study, the Generalized Anxiety Disorder Scale (GAD-7) and the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC-25) were used to explore the mental health level of HQHPs. Meanwhile, the mediating effect of resilience was explored and verified with the bootstrap method or the structural equation model. Results: 20 HQHPs participated in the qualitative study. Two themes were identified in terms of the factors that influenced the HQHPs' mental health levels. The positive factors include optimism, family company, and connection with friends, while the negative factors include inadequate supplies, inadequate information, and other emergencies. 210 HQHPs participated in the quantitative study, with a median resilience score of 66 [55.75, 74] in the lowest score range and an anxiety score of 5 [2, 7] in the mild anxiety range. The correlation analysis showed that nine of the 10 influencing factors identified in qualitative research were positively correlated with CD-RISC-25 scores and negatively correlated with the GAD-7 score. The mediating effect of resilience on anxiety was significant (95% bootstrap CI [-1.818, -0.384], p<0.001; or 95% bootstrap CI [-1.174, -0.430], p<0.001). Conclusion: Even in the post-epidemic era, hospital pharmacists face psychological challenges. They actively address these issues based on accumulated experience and a stabilized mindset. In this process, resilience plays a significant mediating role.

The origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis.

BACKGROUND: Vitamin B12 is essential to human but the implications of serum vitamin B12 level for mortality in clinical practice remain unclear. We conducted a systematic review and dose-response meta-analysis to quantify the relationship between vitamin B12 levels and the risk of all-cause, cardiovascular, and cancer mortality. METHODS: Electronic databases of PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials were searched from inception through May 2023. Two reviewers independently extracted individual study data and evaluated the risk of bias among the studies using the Newcastle‒Ottawa Scale. To examine a potential nonlinear relationship between the vitamin B12 levels and all-cause mortality, we performed a two-stage random effects dose‒response meta-analysis. RESULTS: Twenty-two cohort studies (92,346 individuals with 10,704 all-cause deaths) were included. A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78). Current evidence was mixed for the association between serum vitamin B12 concentration and cardiovascular mortality and was limited for cancer mortality. The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01), CVD mortality (adjusted HR 2.04, 95 % CI 0.99 to 4.19; n = 2; p = 0.02), except cancer mortality (adjusted HR 1.56, 95 % CI 0.82 to 2.95; n = 3). Similarly, serum vitamin B12 concentrations (400-600 pmol/L) were associated with increased all-cause mortality (adjusted HR 1.34, 95 % CI 1.10 to 1.64; n = 9; p < 0.01). CONCLUSIONS: Serum vitamin B12 concentration was positively associated with the risk of all-cause mortality, especially among older adults, with a linear increasing trend. These findings suggested the primary cause of elevated level of serum vitamin B12 concentration should be timely identified and effectively managed in clinical practice.

Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis. Moreover, pharmacological inhibition of PKMYT1 shows efficacy in multiple PDAC cell models and effectively induces tumor regression without overt toxicity in PDAC cell line-derived xenograft and in more clinically relevant patient-derived xenograft models. Mechanistically, in addition to its canonical function of phosphorylating CDK1, PKMYT1 functions as an oncogene to promote PDAC tumorigenesis by regulating PLK1 expression and phosphorylation. Finally, TP53 function and PRKDC activation are shown to modulate the sensitivity to PKMYT1 inhibition. These results define PKMYT1 dependency in PDAC and identify potential therapeutic strategies for clinical translation.

Surface molecularly imprinted polymers-based electrochemical sensor for bovine hemoglobin recognition.

A novel electrochemical sensor for bovine hemoglobin (BHb) recognition and detection was prepared by a surface molecularly imprinted technique. Aldehyde group-functionalized silica microspheres were modified on an Au electrode surface, and these were subsequently covalently bound with the template molecule, BHb, through imine bonds. Electropolymerization was performed to deposit polypyrrole onto the above modified electrode surface. A three-dimensional macroporous structural sensor was obtained after etching of silica and the extraction of BHb. Differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were employed to characterize the fabrication process of the sensor using [Fe(CN)6](3-)/[Fe(CN)6](4-) as an electroactive probe. Since all imprinted cavities were situated at the surface of the polymers, the prepared sensor exhibited considerably fast binding kinetics. Compared to other non-template proteins, the sensor showed an excellent recognition capacity for BHb. Moreover, the prepared sensor also exhibited a dependent relationship between the concentration of BHb and the peak current of [Fe(CN)6](3-)/[Fe(CN)6](4-).