Association between threat-related adverse childhood experiences and chronic lung diseases in a middle and older aged population: A cross-sectional and longitudinal study in China.

OBJECTIVES: We investigated the association between threat-related adverse childhood experiences (ACEs) and the risk of chronic lung diseases (CLDs). METHODS: The data used for this study were extracted from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey of respondents recruited from 450 villages/urban communities in 28 provinces. Threat-related ACEs were constructed using five adverse factors: household substance abuse, physical abuse, domestic violence, unsafe neighbourhood, and bullying). Participants were divided into three groups according to their number of threat-related ACEs at baseline and at follow-up. The association between threat-related ACEs and CLD prevalence in the cross-sectional study was calculated using logistic regression models. The association between threat-related ACEs and CLD onset was evaluated using Cox proportional regression models in the cohort study. Potential confounders were considered in both the cross-sectional and cohort studies. RESULTS: The CLD prevalence in the total population, no exposure group, exposure to one threat-related ACE, and exposure to at least two threat-related ACEs were 10.07% (1320/13104), 9.20% (665/7232), 10.89% (421/3865), and 11.66% (234/2007), respectively. Exposure to one threat-related ACE (OR: 1.23, 95% CI: 1.07-1.41) and exposure to at least two threat-related ACEs (OR: 1.31, 95% CI: 1.11-1.55) were significantly associated with higher CLD prevalence rates. The cohort study included 11,645 participants. During the 7-year follow-up, 738 CLD incidents were identified. Similarly, exposure to one threat-related ACE (HR: 1.20, 95% CI: 1.01-1.43) and at least two threat-related ACEs (HR: 1.64, 95% CI: 1.35-2.00) were significantly associated with a higher CLD incidence risk. CONCLUSIONS: Exposure to threat-related ACEs was significantly associated with a higher CLD prevalence risk and onset. It is crucial to identify individuals who have encountered childhood threats and prioritise the monitoring of their pulmonary function.

Multi-strategy learning-based particle swarm optimization algorithm for COVID-19 threshold segmentation.

With advancements in science and technology, the depth of human research on COVID-19 is increasing, making the investigation of medical images a focal point. Image segmentation, a crucial step preceding image processing, holds significance in the realm of medical image analysis. Traditional threshold image segmentation proves to be less efficient, posing challenges in selecting an appropriate threshold value. In response to these issues, this paper introduces Inner-based multi-strategy particle swarm optimization (IPSOsono) for conducting numerical experiments and enhancing threshold image segmentation in COVID-19 medical images. A novel dynamic oscillatory weight, derived from the PSO variant for single-objective numerical optimization (PSOsono) is incorporated. Simultaneously, the historical optimal positions of individuals in the particle swarm undergo random updates, diminishing the likelihood of algorithm stagnation and local optima. Moreover, an inner selection learning mechanism is proposed in the update of optimal positions, dynamically refining the global optimal solution. In the CEC 2013 benchmark test, PSOsono demonstrates a certain advantage in optimization capability compared to algorithms proposed in recent years, proving the effectiveness and feasibility of PSOsono. In the Minimum Cross Entropy threshold segmentation experiments for COVID-19, PSOsono exhibits a more prominent segmentation capability compared to other algorithms, showing good generalization across 6 CT images and further validating the practicality of the algorithm.

Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer.

BACKGROUND: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. RESULT: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.

Association of frailty with mortality in cancer survivors: results from NHANES 1999-2018.

Cancer survivors are vulnerable to frailty. While few studies have focused on the association of frailty with mortality risk among cancer survivors, the current study aimed to reveal this association. In this cohort study, 4723 cancer survivors were enrolled from the National Health and Nutrition Examination Surveys (NHANES, 1999-2018). Frailty status was quantified using the 53-item frailty index. Death outcomes were linked to National Death Index mortality data (as of December 31, 2019). Cox proportional hazard models were used to estimate HRs (95% CIs). The median (IQR) frailty score was 0.190 (0.132, 0.277). During the median follow-up of 6.7 years, 1775 all-cause deaths (including 581 cancer deaths and 385 cardiac deaths) were documented. Compared to the lowest tertile of frailty scores, the adjusted HRs (95% CIs) for the highest tertile were 2.698 (2.224, 3.272) for all-cause mortality (P trend < 0.001), 2.145 (1.547, 2.973) for cancer mortality (P trend < 0.001), and 3.735 (2.231, 6.251) for cardiac mortality (P trend < 0.001). Moreover, a positive dose‒response association between the frailty score and mortality risk was determined. Each per-unit increase in the frailty score (natural logarithm transformed) was found to increase all-cause mortality by 159% (P < 0.001), cancer mortality by 103% (P < 0.001), and cardiac mortality by 256% (P < 0.001). A consistent result was shown when stratifying by age, sex, race, body mass index, and type of cancer. This study suggested that the frailty index was positively associated with all-cause mortality and cause-specific mortality (including cancer and cardiac deaths) among cancer survivors.

In-situ construction defect-rich CuNiCoS4 /1T-MoS2 heterostructures as superior electrocatalysts for water splitting.

Rational design and construction of bifunctional heterostructure electrocatalysts with high-conductivity and more active sites is imperative for water splitting. Herein, based on the tunable property of layered double hydroxide laminates cations, topological transformation technology and template confine method, a series of high-performance bifunctional catalysts composed of transition metal doping NiCo2S4 (MNiCoS4, M = Cu, Fe, Zn, Mn) and 1T-MoS2 were in-situ fabricated on nickel foam. In particular, CuNiCoS4/1T-MoS2 exhibits an ultralow overpotential of 163 mV at 50 mA cm-2 for oxygen evolution reaction (OER) and favorable hydrogen evolution reaction activity. The two-electrode system requires only 1.52 V to attain a current density of 10 mA cm-2. To the best of our knowledge, its OER electrocatalytic activity far exceed state-of-art catalysts reported. The outstanding performance of this series of catalysts can be attributed to two aspects. First, the highly conductive 1T-MoS2 can facilitate electron transfer, and second, the defect-rich heterostructure can effectively regulate the electronic structure of the active metal and expose abundant active sites. This work provides a valuable strategy for developing high activity electrocatalysts for efficient water splitting.

Clinical relevance, mechanisms, and evolution of polymyxin B heteroresistance carbapenem-resistant Klebsiella pneumoniae: A genomic, retrospective cohort study.

OBJECTIVES: To study the clinical relevance, mechanisms, and evolution of polymyxin B (POLB) heteroresistance (PHR) in carbapenem-resistant Klebsiella pneumoniae (CRKP), potentially leading to a significant rise in POLB full resistant (FR) CRKP. METHODS: Total of 544 CRKP isolates from 154 patients treated with POLB were categorized into PHR and POLB non-heteroresistance (NHR) groups. We performed statistical analysis to compare clinical implications and treatment responses. We employed whole-genome sequencing, bioinformatics, and PCR to study the molecular epidemiology, mechanisms behind PHR, and its evolution into FR. RESULTS: We observed a considerable proportion (118 of 154, 76.62%) of clinically undetected PHR strains before POLB exposure, with a significant subset of them (33 of 118, 27.97%) evolving into FR after POLB treatment. We investigated the clinical implications, epidemiological characteristics, mechanisms, and evolutionary patterns of PHR strains in the context of POLB treatment. About 92.86% (39 of 42) of patients had PHR isolates before FR, highlighting the clinical importance of PHR. the ST15 exhibited a notably lower PHR rate (1 of 8, 12.5% vs. 117 of 144, 81.25%; p < 0.01). The ST11 PHR strains showing significantly higher rate of mgrB mutations by endogenous insertion sequences in their resistant subpopulation (RS) compared with other STs (78 of 106, 73.58% vs. 4 of 12, 33.33%; p < 0.01). The mgrB insertional inactivation rate was lower in FR isolates than in the RS of PHR isolates (15 of 42, 35.71% vs. 84 of 112, 75%; p < 0.01), whereas the pmrAB mutation rate was higher in FR isolates than in the RS of PHR isolates (8 of 42, 19.05% vs. 2 of 112, 1.79%; p < 0.01). The evolution from PHR to FR was influenced by subpopulation dynamics and genetic adaptability because of hypermutability. DISCUSSION: We highlight significant genetic changes as the primary driver of PHR to FR in CRKP, underscoring polymyxin complexity.

Over 5 × 103-Fold Enhancement of Responsivity in Ga2O3-Based Solar Blind Photodetector via Acousto-Photoelectric Coupling.

The emergence of the wide-band-gap semiconductor Ga2O3 has propelled it to the forefront of solar blind detection activity owing to its key features. Although various architectures and designs of Ga2O3-based solar blind photodetectors have been proposed, their performance still falls short of commercial standards. In this study, we demonstrate a method to enhance the performance of a simple metal-semiconductor-metal-structured Ga2O3-based solar blind photodetector by exciting acoustic surface waves. Specifically, we demonstrate that under a bias voltage of 100 mV and a radio frequency signal of 20 dBm, the responsivity and detectivity can increase from 2.78 to 1.65 × 104 A/W and from 8.35 × 1014 to 2.66 × 1016 jones, respectively, rivaling a commercial photomultiplier tube. The over 5 × 103-fold enhancement in responsivity could be attributed to the acousto-photoelectric coupling mechanism. Furthermore, since surface acoustic waves can also serve as signal receivers, such photodetectors offer the prospect of dual-mode detection. Our findings reveal a promising pathway for achieving high-performance Ga2O3-based electronics and optoelectronics.

The effects of amino acid substitution of spike protein and genomic recombination on the evolution of SARS-CoV-2.

Over three years' pandemic of 2019 novel coronavirus disease (COVID-19), multiple variants and novel subvariants have emerged successively, outcompeted earlier variants and become predominant. The sequential emergence of variants reflects the evolutionary process of mutation-selection-adaption of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Amino acid substitution/insertion/deletion in the spike protein causes altered viral antigenicity, transmissibility, and pathogenicity of SARS-CoV-2. Early in the pandemic, D614G mutation conferred virus with advantages over previous variants and increased transmissibility, and it also laid a conservative background for subsequent substantial mutations. The role of genomic recombination in the evolution of SARS-CoV-2 raised increasing concern with the occurrence of novel recombinants such as Deltacron, XBB.1.5, XBB.1.9.1, and XBB.1.16 in the late phase of pandemic. Co-circulation of different variants and co-infection in immunocompromised patients accelerate the emergence of recombinants. Surveillance for SARS-CoV-2 genomic variations, particularly spike protein mutation and recombination, is essential to identify ongoing changes in the viral genome and antigenic epitopes and thus leads to the development of new vaccine strategies and interventions.

Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression.

Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon-λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization.

Background: Many existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics. Methods: Summary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated. Results: In the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019). Conclusion: Our study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

Innate and adaptive immunity to SARS-CoV-2 and predisposing factors.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has affected all countries worldwide. Although some symptoms are relatively mild, others are still associated with severe and even fatal clinical outcomes. Innate and adaptive immunity are important for the control of SARS-CoV-2 infections, whereas a comprehensive characterization of the innate and adaptive immune response to COVID-19 is still lacking and the mechanisms underlying immune pathogenesis and host predisposing factors are still a matter of scientific debate. Here, the specific functions and kinetics of innate and adaptive immunity involved in SARS-CoV-2 recognition and resultant pathogenesis are discussed, as well as their immune memory for vaccinations, viral-mediated immune evasion, and the current and future immunotherapeutic agents. We also highlight host factors that contribute to infection, which may deepen the understanding of viral pathogenesis and help identify targeted therapies that attenuate severe disease and infection.

Si-integrated lanthanide-doped ferroelectrics for a photomemory based on a photochromic reaction.

We describe a Si-integrated photochromic photomemory based on lanthanide-doped ferroelectric Na0.5Bi2.5Nb2O9:Er3+ (NBN:Er) thin films. We show that upconversion emission can be effectively modulated by up to 78% through the photochromic reaction. The coupling between lanthanide upconversion emission and the photochromic effect ensures rewritable and nondestructive readout characteristics. Moreover, integrating photochromic thin films with Si would benefit from its compatibility with the mature complementary metal-oxide semiconductor (CMOS) technique. These results demonstrate the opportunity to develop more compact photochromic photomemories and related photonic devices.

The diagnosis and treatment for a patient with cancer of unknown primary: A case report.

Background: Cancer of unknown primary (CUP) is a class of metastatic malignant tumors whose primary location cannot be determined. The diagnosis and treatment of CUP are a considerable challenge for clinicians. Herein, we report a CUP case whose corresponding primary tumor sites were successfully identified, and the patient received proper treatment. Case report: In February 2022, a 74-year-old woman was admitted to the Medical Oncology Department at Sir Run Run Shaw Hospital for new lung and intestinal tumors after more than 9 years of breast cancer surgery. After laparoscopically assisted right hemicolectomy, pathology revealed mucinous adenocarcinoma; the pathological stage was pT2N0M0. Results from needle biopsies of lung masses suggested poorly differentiated cancer, ER (-), PR (-), and HER2 (-), which combined with the clinical history, did not rule out metastatic breast cancer. A surgical pathology sample was needed to determine the origin of the tumor tissue, but the patient's chest structure showed no indications for surgery. Analysis of the tumor's traceable gene expression profile prompted breast cancer, and analysis of next-generation amplification sequencing (NGS) did not obtain a potential drug target. We developed a treatment plan based on comprehensive immunohistochemistry, a gene expression profile, and NGS analysis. The treatment plan was formulated using paclitaxel albumin and capecitabine in combination with radiotherapy. The efficacy evaluation was the partial response (PR) after four cycles of chemotherapy and two cycles combined with radiotherapy. Conclusion: This case highlighted the importance of identifying accurate primary tumor location for patients to benefit from treatment, which will provide a reference for the treatment decisions of CUP tumors in the future.

Potential Role of the Fragile Histidine Triad in Cancer Evo-Dev.

Cancer development follows an evolutionary pattern of "mutation-selection-adaptation" detailed by Cancer Evolution and Development (Cancer Evo-Dev), a theory that represents a process of accumulating somatic mutations due to the imbalance between the mutation-promoting force and the mutation-repairing force and retro-differentiation of the mutant cells to cancer initiation cells in a chronic inflammatory microenvironment. The fragile histidine triad (FHIT) gene is a tumor suppressor gene whose expression is often reduced or inactivated in precancerous lesions during chronic inflammation or virus-induced replicative stress. Here, we summarize evidence regarding the mechanisms by which the FHIT is inactivated in cancer, including the loss of heterozygosity and the promoter methylation, and characterizes the role of the FHIT in bridging macroevolution and microevolution and in facilitating retro-differentiation during cancer evolution and development. It is suggested that decreased FHIT expression is involved in several critical steps of Cancer Evo-Dev. Future research needs to focus on the role and mechanisms of the FHIT in promoting the transformation of pre-cancerous lesions into cancer.

Evaluation the effectiveness of the Jiangniaosuan formulation in the treatment of hyperuricemic nephropathy in patients with chronic kidney disease stages 3-4: Study protocol of a randomized controlled trial.

Background: Hyperuricemic nephropathy is a highly prevalent kidney disease induced by excessive accumulation and deposition of monosodium urate in kidney, which contributes to the loss of kidney function. The Jiangniaosuan formulation (JNSF) is a Chinese herbal medicine treatment. The aim of this study is to evaluate its efficacy and safety among patients with hyperuricemic nephropathy at chronic kidney disease (CKD) stages 3-4 and with obstruction of phlegm turbidity and blood stasis syndrome. Methods: Our research is designed as a single-centre, double-blinded, randomized, placebo-controlled trial for 118 patients diagnosed with hyperuricemic nephropathy at CKD stages 3-4 and with obstruction of phlegm turbidity and blood stasis syndrome in mainland China. Patients are to be randomized into two groups: either the intervention group which receives JNSF 20.4 g/day combined with febuxostat 20-40 mg/day, or the control group which receives JNSF placebo 20.4 g/day combined with febuxostat 20-40 mg/day. The intervention will be carried on for 24 weeks. The change in estimated glomerular filtration rate (eGFR) is set as the primary outcome. Secondary outcomes include changes in serum uric acid, serum nitric oxide, urinary albumin/creatinine ratio, urinary N-acetyl-ß-D glucosaminidase, urinary ß2 microglobulin, urinary retinol binding protein and TCM syndromes in 24 weeks. Statistical analysis will be formulated by SPSS 24.0. Discussion: The trial will conduce to the comprehensive assessment in the efficacy and safety of JNSF among patients diagnosed with hyperuricemic nephropathy at CKD stages 3-4, and provide a clinical method available on systems of the combination of modern medicine and TCM.

Enhanced gain and detectivity of unipolar barrier solar blind avalanche photodetector via lattice and band engineering.

Ga2O3-based solar blind avalanche photodetectors exhibit low voltage operation, optical filter-free and monolithic integration of photodetector arrays, and therefore they are promising to be an alternative to the bulky and fragile photomultiplier tubes for weak signal detection in deep-ultraviolet region. Here, by deliberate lattice and band engineering, we construct an n-Barrier-n unipolar barrier avalanche photodetector consisting of ß-Ga2O3/MgO/Nb:SrTiO3 heterostructure, in which the enlarged conduction band offsets fortify the reverse breakdown and suppress the dark current while the negligible valance band offsets faciliate minority carrier flow across the heterojunction. The developed devices exhibit record-high avalanche gain up to 5.9 × 105 and detectivity of 2.33 × 1016 Jones among the reported wafer-scale grown Ga2O3-based photodetectors, which are even comparable to the commercial photomultiplier tubes. These findings provide insights into precise manipulation of band alignment in avalanche photodetectors, and also offer exciting opportunities for further developing high-performance Ga2O3-based electronics and optoelectronics.

Unrevealing Temporal Mechanoluminescence Behaviors at High Frequency via Piezoelectric Actuation.

Mechanoluminescence (ML) materials present widespread applications. Empirically, modulation for a given ML material is achieved by application of programmed mechanical actuation with different amplitude, repetition velocity and frequency. However, to date modulation on the ML is very limited within several to a few hundred hertz low-frequency actuation range, due to the paucity of high-frequency mechanical excitation apparatus. The universality of temporal behavior and frequency response is an important aspect of ML phenomena, and serves as the impetus for much of its applications. Here, we push the study on ML into high-frequency range (∼250 kHz) by combining with piezoelectric actuators. Two representative ML ZnS:Mn and ZnS:Cu, Al phosphors were chosen as the research objects. Time-resolved ML of ZnS:Mn and ZnS:Cu, Al shows unrevealed frequency-dependent saturation and quenching, which is associated with the dynamic processes of traps. From the point of applications, this study sets the cut-off frequency for ML sensing. Moreover, by in-situ tuning the strain frequency, ZnS:Mn exhibits reversible frequency-induced broad red-shift into near-infrared range. These findings offer keen insight into the photophysics nature of ML and also broaden the physical modulation of ML by locally adjusting the excitation frequency.