ABSTRACT
The water and sediment samples were collected from the Yu River and Taowanbei River during periods of summer and winter. The NCPI, EWQI, Igeoand PERI were used to evaluate the pollution degree and cumulative ecological risk of HMs in the water and sediments. The PMF model was used to analyze the sources of HMs in river sediments. The pollution degree of Cd, Hg and Zn in the water reached the severe pollution level, in the rank of Hg > Zn > Cd. Cd and Zn in sediments are heavily polluted, Cu is lightly polluted, Pb and As are within the warning range, and the pollution rank is Cd > Zn > Cu > Pb > As. The cumulative ecological risk of HMs in sediments reached extremely strong level, mainly Cd and Hg. The main sources of HMs in sediments are mining sources, mixed agricultural and transport sources, and natural sources, which contributed 42.1 %, 34.1 % and 23.8 %, respectively.
Subject(s)
Environmental Monitoring , Geologic Sediments , Metals, Heavy , Mining , Molybdenum , Rivers , Water Pollutants, Chemical , Metals, Heavy/analysis , China , Water Pollutants, Chemical/analysis , Geologic Sediments/chemistry , Rivers/chemistry , Molybdenum/analysis , Risk AssessmentABSTRACT
Se alloying has enabled significantly higher carrier lifetimes and photocurrents in CdTe solar cells, but these benefits can be highly dependent on CdSexTe1-x processing. This work evaluates the optoelectronic, chemical, and electronic properties of thick (3 µm) undoped CdSexTe1-x of uniform composition and varied processing conditions (CdSexTe1-x evaporation rate, CdCl2 anneal, Se content) chosen to reflect various standard device processing conditions. Sub-bandgap defect emission is observed, which increased as Se content increased and with "GrV-optimized CdCl2" (i.e., CdCl2 anneal conditions used for group-V-doped devices). Low carrier lifetime is found for GrV-optimized CdCl2, slow CdSexTe1-x deposition, and low-Se films. Interestingly, all films (including CdTe control) exhibited n-type behavior, where electron density increased with Se up to an estimated ≈1017 cm-3. This behavior appears to originate during the CdCl2 anneal, possibly from Se diffusion leading to anion vacancy (e.g., VSe, VTe) and ClTe generation.
ABSTRACT
Constructing a highly localized wave field by means of bound states in the continuum (BICs) promotes enhanced wave-matter interaction and offers approaches to high-sensitivity devices. Elastic waves can carry complex polarizations and thus differ from electromagnetic waves and other scalar mechanical waves in the formation of BICs, which is yet to be fully explored and exploited. Here, we report the investigation of local resonance modes supported by a Lamb waveguide side-branched with two pairs of resonant pillars and show the emergence of two groups of elastic BICs with different polarizations or symmetries. Particularly, the two groups of BICs exhibit distinct responses to external perturbations, based on which a label-free sensing scheme with enhanced-sensitivity is proposed. Our study reveals the rich properties of BICs arising from the complex wave dynamics in elastic media and demonstrates their unique functionality for sensing and detection.
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Malaria is caused by an apicomplexan protozoan parasite, Plasmodium, and is transmitted through vectors. It remains a substantial health burden, especially in developing countries, leading to significant socioeconomic losses. Although the World Health Organization (WHO) has approved various antimalarial medications in the past two decades, the increasing resistance to these medications has worsened the situation. The development of drug resistance stems from genetic diversity among Plasmodium strains, impeding eradication efforts. Consequently, exploring innovative technologies and strategies for developing effective medications based on the host is crucial. Artemisinin and its derivatives (artemisinins) have been recommended by the WHO for treating malaria owing to their known effectiveness in killing the parasite. However, their potential to target the host for malaria treatment has not been investigated. This article concisely reviews the application of host-directed therapeutics, potential drug candidates targeting the host for treating malaria, and usage of artemisinins in numerous diseases. It underscores the importance of host-directed interventions for individuals susceptible to malaria, suggests the potential utility of artemisinins in host-directed malaria treatments, and posits that the modulation of host proteins with artemisinins may offer a means of intervening in host-parasite interactions. Further studies focusing on the host-targeting perspective of artemisinins can provide new insights into the mechanisms of artemisinin resistance and offer a unique opportunity for new antimalarial drug discovery.
Subject(s)
Antimalarials , Artemisinins , Malaria , Artemisinins/pharmacology , Artemisinins/therapeutic use , Humans , Antimalarials/pharmacology , Antimalarials/therapeutic use , Malaria/drug therapy , Animals , Drug Resistance/drug effects , Plasmodium/drug effects , Host-Parasite Interactions/drug effectsABSTRACT
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is characterized by highly genetic heterogeneity, owing to recurrent fusion genes, gene mutations, intragenic deletion, and gene overexpression, which poses significant challenges in clinical detection. RNA sequencing (RNA-seq) is a powerful tool for detecting multiple genetic abnormalities, especially cryptic gene rearrangements, in a single test. METHODS: Sixty samples (B-ALL, n = 49; T-ALL, n = 9; mixed phenotype acute leukemia (MPAL), n = 2) and 20 controls were analyzed by targeted RNA-seq panel of 507 genes developed by our lab. Of these, 16 patients were simultaneously analyzed for gene mutations at the DNA level using a next-generation sequencing panel of 51 genes. Fusion genes, CRLF2 expression, and IKZF1 intragenic deletion were also detected by reverse transcription-polymerase chain reaction (RT-PCR). Karyotype analysis was performed using the R-banding and G-banding technique on bone marrow cells after 24 hours of culture. Partial fusion genes were analyzed using fluorescence in situ hybridization (FISH). RESULTS: Compared with the results of Karyotype analysis, FISH, and RT-PCR, the detection rate of fusion genes by targeted RNA-seq increased from 48.3% to 58.3%, and six unexpected fusion genes were discovered, along with one rare isoform of IKZF1 intragenic deletion (IK10). The DNA sequencing analysis of 16 ALL patients revealed that 96.2% (25/26) of gene mutations identified at the DNA level were also detectable at the RNA level, except for one mutation with a low variant allele fraction. The detection of CRLF2 overexpression exhibited complete concordance between RT-PCR and RNA-seq. CONCLUSION: The utilization of RNA-seq enables the identification of clinically significant genetic abnormalities that may go undetected through conventional detection methods. Its robust analytical performance might bring great application value for clinical diagnosis, prognosis, and therapy in ALL.
Subject(s)
Ikaros Transcription Factor , Mutation , Oncogene Proteins, Fusion , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Cytokine , Humans , Ikaros Transcription Factor/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Male , Female , Receptors, Cytokine/genetics , Child , Oncogene Proteins, Fusion/genetics , Adult , Gene Expression Regulation, Leukemic , Adolescent , Child, Preschool , Middle Aged , Sequence Analysis, RNA , Gene Deletion , High-Throughput Nucleotide SequencingABSTRACT
BACKGROUND: Benzodiazepines (BZD) and Z-drugs are often prescribed for alleviating such symptoms and treating maternal psychiatric disorders and epilepsy. However, their use is limited due to the apprehensions and risks related to poor maternal and neonatal outcomes. OBJECTIVE: This meta-analysis evaluated the rationality and efficacy of using Benzodiazepines and Z-drugs for managing anxiety and depression in pregnant women. METHODS: The meta-analysis was based on a systematic review through keyword search utilizing Scopus, Pubmed, and Cochrane databases. One hundred three articles were deemed eligible, but only 21 articles were selected for the meta-analysis. RESULTS: The meta-analysis showed that despite the indication for anxiety and depression in pregnant women, the usage of BZD and Z-drugs was significantly low compared to other psychotropic medications, with no therapy or non-pharmacological interventions. Our study shows that, during the antenatal and postnatal period, women required more anti-depressants, anti-psychotics, and anxiolytic drugs. CONCLUSION: Although BZDs and Z-drugs are effective in managing insomnia during peripartum and post-partum, they are either ineffective or contraindicated for managing anxiety and depression in pregnant women compared to anxiolytics and anti-depressants.
ABSTRACT
Five undescribed compounds, including two cholestane glycosides parispolyosides A and E, and three spirostanol glycosides parispolyosides B-D, were isolated from rhizome of Paris polyphylla var. chinensis (Franch.) Hara, together with twenty-one known steroidal saponins. Their chemical structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. Two of these compounds demonstrated potent inhibitory effect on NO production stimulated by lipopolysaccharide in raw 264.7 cells with IC50 values of 61.35 µM and 37.23 µM. Four compounds exhibited moderate inhibitory activity against HepG2 cells with IC50 values ranging from 9.43 to 24.54 µM. Molecular docking analysis revealed that the potential mechanism of NO inhibition by the active compounds was associated with the interactions with iNOS protein.
Subject(s)
Antineoplastic Agents , Liliaceae , Saponins , Rhizome/chemistry , Molecular Docking Simulation , Saponins/chemistry , Liliaceae/chemistry , Anti-Inflammatory Agents/pharmacologyABSTRACT
Tongue cancer has a very high incidence in China, and there is a need to develop new anti-tumour drugs against it. We synthesised 31 novel quinoline derivatives to test their anti-tumour activity. A compound referred to as "f25" was identified through screening for its high in vitro toxicity against an oral squamous carcinoma cell line (CAL-27). f25 exhibited significant cytotoxicity against CAL-27 cells (IC50 = 7.70 ± 0.58 µΜ). f25 also inhibited the migration and invasion of CAL-27 cells to a level comparable with that of the chemotherapy agent cisplatin. Moreover, f25 promoted the apoptosis of CAL-27 cells. Transcriptome sequencing and western blotting showed that the mechanism of action of f25 against CAL-27 cells involved the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Specifically, f25 could bind to PPAR-α, PPAR-ß, and PPAR-γ and increase their expression. In vivo experiments showed that treatment with f25 led to a reduction in tumour volume in nude mice without significant toxicity. Overall, this study highlights the potential of quinoline compounds (particularly f25) for the design and synthesis of anti-tumour drugs. It also underscores the importance of the PPAR signalling pathway as a target for potential cancer therapies.
Subject(s)
Antineoplastic Agents , Quinolines , Tongue Neoplasms , Mice , Animals , Tongue Neoplasms/drug therapy , Mice, Nude , Cell Line, Tumor , Antineoplastic Agents/pharmacology , PPAR gamma/metabolism , Neoplasm Invasiveness/prevention & control , Quinolines/pharmacology , Tongue/metabolismABSTRACT
This research aimed to distinguish person minimization from emotion minimization in Chinese families with adolescent children. In Study 1, a scale was developed to assess two types of minimization through expert evaluations (Mage = 35.05 years, 89.47% females) and factor analyses of mothers' reported minimization (n = 417, Mage = 42.73 years). Study 2 showed that person minimization related to adolescents' (n = 412, Mage = 13.91 years, 44.11% females) and mothers' socioemotional dysfunction and mothers' (n = 412, Mage = 41.17 years) nonsupportive responses; emotion minimization correlated with adolescents' and mothers' cognitive reappraisal and expressive suppression, and mothers' supportive responses. In Study 3, an experimental design was used, dividing adolescents into two groups: one group (n = 137, Mage = 12.64 years, 55.33% females) evaluating emotion minimization and the other group (n = 123, Mage = 12.74 years, 52.26% females) evaluating person minimization. The results showed that adolescents rated emotion minimization more positively than person minimization. Study 4 (n = 200, Mage = 13.85, 34.50% females) showed reciprocal relations between problematic communication patterns of adolescents' emotional distress and person minimization over time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
ABSTRACT
The self, like the concept of central "gravity", facilitates the processing of information that is directly relevant to the self. This phenomenon is known as the self-prioritization effect. However, it remains unclear whether the self-prioritization effect extends to the processing of emotional facial expressions. To fill this gap, we used a self-association paradigm to investigate the impact of self-relevance on the recognition of emotional facial expressions while controlling for confounding factors such as familiarity and overlearning. Using a large and diverse sample, we replicated the effect of self-relevance on face processing but found no evidence for a modulation of self-relevance on facial emotion recognition. We propose two potential theoretical explanations to account for these findings and emphasize that further research with different experimental designs and a multitasks measurement approach is needed to understand this mechanism fully. Overall, our study contributes to the literature on the parallel cognitive processing of self-relevance and facial emotion recognition, with implications for both social and cognitive psychology.
Subject(s)
Facial Expression , Facial Recognition , Emotions , Recognition, Psychology , Research DesignABSTRACT
The aim of this research is to investigate which CALL glossing modes (text only, text plus audio, and text plus video clips) are effective for learners' idiom acquisition. Ninety-nine intermediate-level first-year students from a university in China were divided into three groups. In order to determine if CALL glossing had any effect on students' idiom learning, pre- and post-idiom tests were administered. In addition, all the participants completed a questionnaire and five participants from each group completed face-to-face interviews to understand learners' perceptions of different CALL glosses. The results indicated that all three glossing modes promoted idiom acquisition; specifically, text with video glossing mode was more effective than text plus audio glosses and text only glossing mode. These results offer pedagogical implications for idiom teaching and learning, and also provide valuable insights for education in the future.
Subject(s)
Learning , Students , Humans , Educational Status , China , UniversitiesABSTRACT
Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter's increased risk for urinary tract cancers.
Subject(s)
Firefighters , Fires , Urologic Neoplasms , Humans , Aspartic Acid , Uremic Toxins , Metabolome , Metabolomics/methods , ProlineABSTRACT
Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Subject(s)
Antimalarials , Artemisinins , Cardiovascular Diseases , Heart Failure , Malaria, Cerebral , Quinolines , Child , Adult , Humans , Antimalarials/pharmacology , Cardiovascular Diseases/drug therapy , Artemisinins/pharmacology , Malaria, Cerebral/drug therapy , Heart Failure/drug therapy , Arrhythmias, Cardiac/drug therapyABSTRACT
Intelligent transportation systems (ITS) urgently need to realize vehicle identification, dynamic monitoring, and traffic flow monitoring under high-speed motion conditions. Vehicle tracking based on radio frequency identification (RFID) and electronic vehicle identification (EVI) can obtain continuous observation data for a long period of time, and the acquisition accuracy is relatively high, which is conducive to the discovery of rules. The data can provide key information for urban traffic decision-making research. In this paper, an RFID tag motion trajectory tracking method based on RF multiple features for ITS is proposed to analyze the movement trajectory of vehicles at important checkpoints. The method analyzes the accurate relationship between the RSSI, phase differences, and driving distances of the tag. It utilizes the information weight method to obtain the weights of multiple RF characteristics at different distances. Then, it calculates the center point of the common area where the vehicle may move under multi-antenna conditions, confirming the actual position of the vehicle. The experimental results show that the average positioning error of moving RFID tags based on dual-frequency signal phase differences and RSSI is less than 17 cm. This method can provide real-time, high-precision vehicle positioning and trajectory tracking solutions for ITS application scenarios such as parking guidance, unmanned vehicle route monitoring, and vehicle lane change detection.
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The development of metal halide perovskite/perovskite heterostructures is hindered by rapid interfacial halide diffusion leading to mixed alloys rather than sharp interfaces. To circumvent this outcome, we developed an ion-blocking layer consisting of single-layer graphene (SLG) deposited between the metal halide perovskite layers and demonstrated that it effectively blocks anion diffusion in a CsPbBr3/SLG/CsPbI3 heterostructure. Spatially resolved elemental analysis and spectroscopic measurements demonstrate the halides do not diffuse across the interface, whereas control samples without the SLG show rapid homogenization of the halides and loss of the sharp interface. Ultraviolet photoelectron spectroscopy, DFT calculations, and transient absorbance spectroscopy indicate the SLG has little electronic impact on the individual semiconductors. In the CsPbBr3/SLG/CsPbI3, we find a type I band alignment that supports transfer of photogenerated carriers across the heterointerface. Light-emitting diodes (LEDs) show electroluminescence from both the CsPbBr3 and CsPbI3 layers with no evidence of ion diffusion during operation. Our approach provides opportunities to design novel all-perovskite heterostructures to facilitate the control of charge and light in optoelectronic applications.
ABSTRACT
Enfacement illusions are traditionally elicited by visuo-tactile stimulation, but more active paradigms become possible through the usage of virtual reality techniques. For instance, virtual mirrors have been recently proposed to induce enfacement by visuo-motor stimulation. In a virtual mirror experiment, participants interact with an avatar that imitates their facial movements. The active control over the avatar greatly enhances the sense of agency, which is an important ingredient for successful enfacement illusion induction. Due to technological challenges, most virtual mirrors so far were limited to the imitation of the participant's head pose, i.e., its location and rotation. However, stronger experiences of agency can be expected by an increase in the avatar's mimicking abilities. We here present a new open-source framework for virtual mirror experiments, which we call the Open Virtual Mirror Framework (OVMF). The OVMF can track and imitate a large range of facial movements, including pose and expressions. It has been designed to run on standard computer hardware and easily interfaces with existing toolboxes for psychological experimentation, while satisfying the requirement of a tightly controlled experimental setup. Further, it is designed to enable convenient extension of its core functionality such that it can be flexibly adjusted to many different experimental paradigms. We demonstrate the usage of the OVMF and experimentally validate its ability to elicit experiences of agency over an avatar, concluding that the OVMF can serve as a reference for future experiments and that it provides high potential to stimulate new directions in enfacement research and beyond.
Subject(s)
Illusions , Virtual Reality , Humans , Facial Expression , Illusions/physiology , Movement/physiologyABSTRACT
This research aims to investigate the salience of mothers' emotional expressivity and its links with adolescents' emotional wellbeing and expressivity in an urban society endorsing more individualism and a rural society ascribing to more collectivism. By comparing Chinese urban (N = 283, M age = 14.13) and rural (N = 247, M age = 14.09) adolescents, this research found that urban mothers' expression of positive-dominant and positive-submissive emotions (PD and PS) were more common while expression of negative-dominant (ND) emotions was less common than rural mothers'. PD and PS had significant links with urban and rural adolescents' increased emotional expressivity and self-esteem, however, only significantly related to urban adolescents' decreased depression but not with rural adolescents'. ND had significant links with both urban and rural adolescents' expression of negative emotions, however, only significantly correlated with urban adolescents' less level of self-esteem and rural adolescents' more expression of positive emotions. No significant difference was found in the salience of urban and rural mothers' expression of negative-submissive (NS) emotions, which positively related to both urban and rural adolescents' depression and emotional expressivity. Moreover, we found that adolescents' emotional wellbeing (i.e., self-esteem and depression) mediated the relationship between mothers' emotional expressivity and adolescents' expressivity in both societies. Overall, the study findings document that the salience of mothers' emotional expressivity and its relations with adolescents' emotional adjustment differ between urban and rural societies.
Subject(s)
Mother-Child Relations , Mothers , Female , Humans , Adolescent , Mothers/psychology , Mother-Child Relations/psychology , Emotions , Emotional Adjustment , Self ConceptABSTRACT
Soliton microcombs, offering large mode spacing and broad bandwidth, have enabled a variety of advanced applications, particularly for telecommunications, photonic data center, and optical computation. Yet, the absolute power of microcombs remains insufficient, such that optical power amplification is always required. Here, we demonstrate a combined technique to access power-sufficient optical microcombs, with a photonic-integrated soliton microcomb and home-developed erbium-doped gain fiber. The soliton microcomb is generated in an integrated Si3N4 microresonator chip, which serves as a full-wave probing signal for power amplification. After the amplification, more than 40 comb modes, with 115-GHz spacing, reach the onset power level of >−10 dBm, which is readily available for parallel telecommunications , among other applications.
ABSTRACT
Artificial structures provide an efficient method to generate acoustic vortices carrying orbital angular momentum (OAM) essential for applications ranging from object manipulation to acoustic communication. However, their flexibility in terms of chirality control has thus far been limited by the lack of reconfigurability and degrees of freedom like spin-orbit coupling. Here we show that this restriction can be lifted by controlling the individual on-off states of two coherent monopolar sources inside a passive parity-time-symmetric ring cavity at an exceptional point where the counter-propagating waves coalesce into one chiral eigenmode. One of the sources satisfies the chirality-reversal condition, generating a travelling wave field fully decoupled from and opposite to the chiral eigenmode, while the other source is phase-shifted such that the wave generated by the first source can be canceled out, and the remaining sound field circulates in the same direction as the chiral eigenmode. Such non-Hermitian selective excitation enables our experimental realization of acoustic vortex emission with switchable OAM but free of system reconfiguration. Our work offers opportunities for chiral sound manipulation as well as integrated and tunable acoustic OAM devices.
ABSTRACT
Nontrivial band topologies have been discovered in classical systems and hold great potential for device applications. Unlike photons, sound has fundamentally different dynamics and symmetries in fluids and solids, represented as scalar and vector fields, respectively. So far, searches for topological phononic materials have only concerned sound in either fluids or solids alone, overlooking their intricate interactions in "mixtures". Here, we report an approach for topological phononics employing such unique interplay, and demonstrate the realization of type-II nodal rings, elusive in phononics, in a simple three-dimensional phononic crystal. Type-II nodal rings, as line degeneracies in momentum space with exotic properties from strong tilting, are directly observed through ultrasonic near-field scanning. Strongly tilted drumhead surface states, the hallmark phenomena, are also experimentally demonstrated. This phononic approach opens a door to explore topological physics in classical systems, which is easy to implement that can be used for designing high-performance acoustic devices.