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Abstract Objectives STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. Conclusions In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

Abstract Background Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The major reasons are lack of specific cell surface antigens and complex tumor microenvironment. Here we identify CD22, a well-known tumor surface marker in hematologic malignancies, is expressed in ESCC, possibly serving as a potential target of CAR-NK cell therapy. Methods The expression of 13 tumor cell surface antigens used clinically was analyzed in patients from The Cancer Genome Atlas (TCGA) database. Also, mRNA expression were detected in 2 ESCC cell lines and 2 patients samples by qCPR. Then according to Venn diagram, CD22 was selected for further investigation. Following this, the expression of CD22 by immunofluorescence (IF) in ESCC cell lines and by immunohistochemistry (IHC) in 87 cases of human ESCC samples was detected respectively. On the basis of H-score results, the correlation between CD22 expression and clinical parameters was analyzed. As a proof, the efficacy of CD22-targeted CAR-NK cells against ESCC cell lines was performed by a real-time cell analyzer (RTCA) platform. Results KYSE-140 and KYSE-150 cell lines displayed surface expression of CD22. IHC showed an 80.46% (70/87) positive rate in ESCC patient samples. Among these, cell membranous expression of CD22 was observed in 27.59% (24/87) patient samples. Through chi-square test, expression of CD22 in ESCC was associated with lymph node metastasis while it was no related to the depth of tumor invasion and clinical stage. Engineered CD22-targeted CAR-NK cells exhibited inhibitory growth capability against ESCC cell lines (p

An ultra-sensitive phase plasmonic sensor combined with weak value amplification is proposed for the detection of IgG, as a model analyte. Phase detection is accomplished by self-interference between the p-polarization and the s-polarization of the light. With the principles of weak value amplification, a phase compensator is used to modulate the coupling strength and enhance the refractive index sensitivity of the system. On a simple Au-coated prism-coupled surface plasmon resonance (SPR) structure, the scheme, called WMSPR, achieves a refractive index sensitivity of 4.737 × 104 nm/RIU, which is about three times higher than that of the conventional phase-based approach. The proposed WMSPR biosensor gives great characteristics with a high resolution of 6.333 × 10−8 RIU and a low limit of detection (LOD) of 5.3 ng/mL. The results yield a great scope to promote the optimization of other SPR biosensors for high sensitivity.

IntroductionChimeric antigen receptor natural killer (CAR-NK) cells have been found to be successful in treating hematologic malignancies and present potential for usage in solid tumors.MethodsIn this study, we created CD276-targeted CAR-expressing NK cells from pluripotent stem cells (iPSC CD276-targeted CAR-NK cells) and evaluated their cytotoxicity against esophageal squamous cell carcinoma (ESCC) using patient-specific organoid (PSO) models comprising of both CD276-positive and CD276-negative adjacent epithelium PSO models (normal control PSO, NC PSO) as well as primary culture of ESCC cell models. In addition, in vitro and in vivo models such as KYSE-150 were also examined. iPSC NK cells and NK-free media were used as the CAR-free and NK-free controls, respectively.ResultsThe positive CD276 staining was specifically detected on the ESCC membrane in 51.43% (54/105) of the patients of all stages, and in 51.35% (38/74) of stages III and IV. The iPS CD276-targeted CAR-NK cells, comparing with the iPS NK cells and the NK-free medium, exhibited specific and significant cytotoxic activity against CD276-positive ESCC PSO rather than CD276-negative NC PSO, and exhibited significant cytotoxicity against CD276-expressing cultured ESCC cells, as well as against CD276-expressing KYSE-150 in vitro and in BNDG mouse xenograft.DiscussionThe efficacy of the iPSC CD276-targeted CAR-NK cells demonstrated by their successful treatment of CD276-expressing ESCC in a multitude of pre-clinical models implied that they hold tremendous therapeutic potential for treating patients with CD276-expressing ESCC.

The demand for accurate and efficient immunoassays calls for the development of precise, high-throughput analysis methods. This paper introduces a novel approach utilizing a weak measurement interface sensor for immunoassays, offering a solution for high throughput analysis. Weak measurement is a precise quantum measurement method that amplifies the weak value of a system in the weak interaction through appropriate pre- and post-selection states. To facilitate the simultaneous analysis of multiple samples, we have developed a chip with six flow channels capable of conducting six immunoassays concurrently. We can perform real-time immunoassay to determine the binding characteristics of spike protein and antibody through real-time analysis of the flow channel images and calculating the relative intensity. The proposed method boasts a simple structure, eliminating the need for intricate nano processes. The spike protein concentration and relative intensity curve were fitted using the Log-Log fitting regression equation, and R2 was 0.91. Utilizing a pre-transformation approach to account for slight variations in detection sensitivity across different flow channels, the present method achieves an impressive limit of detection(LOD) of 0.85 ng/mL for the SARS-CoV-2 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, with a system standard deviation of 5.61. Furthermore, this method has been successfully verified for monitoring molecular-specific binding processes and differentiating binding capacities.

IntroductionThe clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. MethodsWe assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively.ResultsMUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. ConclusionThe MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

Identifying the invasive cancer area is a crucial step in the automated diagnosis of digital pathology slices of the breast. When examining the pathological sections of patients with invasive ductal carcinoma, several evaluations are required specifically for the invasive cancer area. However, currently there is little work that can effectively distinguish the invasive cancer area from the ductal carcinoma in situ in whole slide images. To address this issue, we propose a novel architecture named ResMTUnet that combines the strengths of vision transformer and CNN, and uses multi-task learning to achieve accurate invasive carcinoma recognition and segmentation in breast cancer. Furthermore, we introduce a multi-scale input model based on ResMTUnet with conditional random field, named MS-ResMTUNet, to perform segmentation on WSIs. Our systematic experimentation has shown that the proposed network outperforms other competitive methods and effectively segments invasive carcinoma regions in WSIs. This lays a solid foundation for subsequent analysis of breast pathological slides in the future. The code is available at: https://github.com/liuyiqing2018/MS-ResMTUNet

IntroductionIn cancer treatment, every minute counts. Due to the unpredictable behavior of cancer cells caused by continuous mutations, each cancer patient has a unique situation and may or may not respond to a specific drug or treatment. The process of finding an effective therapy can be time-consuming, but cancer patients do not have the luxury of time for trial and error. Therefore, a novel technology to fast generate a patient relevant organoid for the therapies selecting is urgently needed.MethodsUtilizing the new organoid technology by specially dissolving the mesenchyme in tumor tissues acquired from cancer patients, we realized the work of creating patient-specific organoids (PSO) within one day.ResultsPSO properties reflect those of its respective original in vivo tumor tissue and can be utilized to perform various in vitro drug sensitivity tests to identify the most effective clinical treatment for patients. Additionally, PSO can aid in assessing the efficacy of immune cell therapies.DiscussionOrganoid technology has advanced significantly in recent years. However, current cancer organoid methods involve creating 3D tumor tissue from 2D cancer cells or cell clusters, primarily for cancer research purposes aimed at investigating related molecular and cellular mechanisms of tumor development. These methods are research-driven, not tailored towards clinical applications, and cannot provide personalized information for individual patients. PSO filled the gap of clinic-driven and time-saving method for the personalized therapies selecting to the cancer patients.

Abstract Background Esophageal diverticulum is a rare condition that requires treatment only when symptoms are present. Surgery has been considered to be the only curative option for symptomatic cases. The most popular procedure is diverticulectomy. Clear and intact exposure of the diverticulum’s neck is the basis for safe and effective diverticulectomy. Case presentation We herein report a case of a 57 year-old woman with an epiphrenic diverticulum. VATS diverticulectomy was scheduled. To better identify the diverticulum neck, we injected indocyanine green (ICG) into the diverticulum through the endoscopic channel, and the diverticulum wall and neck were clearly visible under near-infrared (NIR) fluorescence. With the help of this method, diverticulectomy was successfully performed. Conclusion This case shows that NIR fluorescence with ICG is safe, simple and reliable and can be used for diverticulectomy.

Background: Glomerular lesion recognition is one of the most crucial steps in the diagnosis of kidney disease. Deep learning, which relies on large numbers of pathology images, assists pathologists to access glomerular lesions more efficiently, objectively and accurately. However, due to different pathological development of glomeruli, complicated lesion patterns, and limited resolution of pathology images, there is annotation noise in datasets, making the deep learning model under- or over-fit. Methods: In this paper, we propose a novel noisy label learning model for lesion recognition in glomerular datasets with annotation noise. The model integrates uncertainty-based noisy label discriminator, contrastive learning, and consistency regularization to achieve high signal-to-noise supervision, pathology feature extraction, and utilization of pathology images. Results: We constructed large-scale glomerular datasets from 870 kidney disease cases using different stainings including Periodic acid-Schiff (PAS), Masson Trichrome (MT) and Periodic Schiff-Methenamine (PASM). Intensive experiments demonstrated the superiority of the proposed model for glomerular lesion recognition compared to other methods, as 25% of the lesions had $f_{1}-score$ above 85%, 43.75% had $f_{1}-score$ above 80%, and 75% had $f_{1}-score$ at or above 70%. Additionally, further experiments demonstrate the effectiveness of each module. Conclusions: The noisy label learning model proposed is able to recognize the most glomerular lesions, with the annotation noise discrimination and large amounts of pathology images utilization, laying the foundation for the development of computer-aided evaluation system for the renal pathology.

Chlorphenamine maleate is a prohibited additive found in herbal teas and health foods. Excessive intake of this substance can result in adverse health effects. In this study, two novel haptens, PEM and bepotastine (PB1), mimicking chlorphenamine maleate structure were designed and synthesized based on molecular simulation for developing two corresponding polyclonal antibodies (PEM-Ab and PB1-Ab), respectively. Afterward, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed to quickly and accurately detect chlorphenamine maleate in herbal teas using PB1-Ab, which has a high sensitivity and specificity. For chlorphenamine maleate, the half-maximal inhibitory concentration (IC50) and limit of detection (LOD) of PB1-Ab under ideal circumstances were found to be 1.18 µg/L and 0.07 µg/L, respectively. Besides, an environmentally friendly sample pre-treatment strategy was employed that allowed easy and effective elimination of complex matrices. The ic-ELISA method observed the average recovery rate from 87.7% to 94.0% with the variance coefficient (CV) ranging from 2.2% to 9.4%. Additionally, the identification of 25 commercially available herbal teas using liquid chromatography-tandem mass spectrometry (LC-MS/MS) further confirmed the validity of our detection. The results of the two methods are consistent. Overall, the proposed ic-ELISA could be an ultrasensitive and reliable method for chlorphenamine maleate adulterated in foods or exposure to the environment.

Summary: Background: Determining the origin of bone metastatic cancer (OBMC) is of great significance to clinical therapeutics. It is challenging for pathologists to determine the OBMC with limited clinical information and bone biopsy. Methods: We designed a regional multiple-instance learning algorithm to predict the OBMC based on hematoxylin-eosin (H&E) staining slides alone. We collected 1041 cases from eight different hospitals and labeled 26,431 regions of interest to train the model. The performance of the model was assessed by ten-fold cross validation and external validation. Under the guidance of top3 predictions, we conducted an IHC test on 175 cases of unknown origins to compare the consistency of the results predicted by the model and indicated by the IHC markers. We also applied the model to identify whether there was tumor or not in a region, as well as distinguishing squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumor. Findings: In the within-cohort, our model achieved a top1-accuracy of 91.35% and a top3-accuracy of 97.75%. In the external cohort, our model displayed a good generalizability with a top3-accuracy of 97.44%. The top1 consistency between the results of the model and the immunohistochemistry markers was 83.90% and the top3 consistency was 94.33%. The model obtained an accuracy of 98.98% to identify whether there was tumor or not and an accuracy of 93.85% to differentiate three types of cancers. Interpretation: Our model demonstrated good performance to predict the OBMC from routine histology and had great potential for assisting pathologists with determining the OBMC accurately. Funding: National Science Foundation of China (61875102 and 61975089), Natural Science Foundation of Guangdong province (2021A15-15012379 and 2022A1515 012550), Science and Technology Research Program of Shenzhen City (JCYJ20200109110606054 and WDZC20200821141349001), and Tsinghua University Spring Breeze Fund (2020Z99CFZ023).

In this study, a method to improve the detection accuracy of a “weak measurement” system of optical rotation was proposed by determining the optimal total phase difference of the system. Analysis of the characteristics of weak measurement regime of the system under different total phase differences provided the total phase difference corresponding to the regime with the smallest ratio of system noise level to sensitivity (that is, the highest system resolution). In this regime, an optical rotation resolution of 5.522 × 10−6° was obtained, which is nearly an order of magnitude higher than the original system.

A multi-channel high-throughput chiral molecule determination method based on weak value amplification (WVA) is proposed for the first time. This method can be used for high-throughput and high-precision determination of chiral molecule. Through the design of multi-channel weak measurement system, we realized the real-time, high-throughput, high-sensitivity and high-resolution detection of chiral molecules by selecting proper measurement states. In this work, we have realized a sensitivity of 11.8 nm/° and a resolution of 3.13 × 10-4° for measuring optical rotation. Moreover, the proposed method is successfully applied for detection of lactose content in milk samples. Furthermore, the system has the advantages of simple and robust real-time detection settings, strong stability, high measurement efficiency and good scalability. This method has important significance in clinical diagnosis, food safety and biological system.

In this work, the difference between the weak measurement method and the weak value amplification process and the classical measurement process is thoroughly discussed, and the transition conditions of the weak value enhancement are obtained. A transition mode of the weak measurement and the classical measurement is proposed for the first time, and a better fitting model of the measurement results is found by performing a systematic analysis. On top of that, the importance of the new fitting method for the application of the weak measurement system is verified during the industrial production of organic molecular -nucleic acid, protein, polysaccharide-hydrolysis or synthesis. At the same time, a variety of spectral characterization methods are proposed and the advantages and disadvantages of the different characterization methods are analyzed through carrying out experiments. Consequently, the wide implementation of weak measurement-based detection technology is attained.

Currently, the world is facing the problem of bacterial resistance, which threatens public health, and bacterial antimicrobial susceptibility testing (AST) plays an important role in biomedicine, dietary safety and aquaculture. Traditional AST methods take a long time, usually 16–24 h, and cannot meet the demand for rapid diagnosis in the clinic, so rapid AST methods are needed to shorten the detection time. In this study, by using an in-house built centrifuge to centrifuge bacteria in a liquid medium onto the inner wall of the bottom surface of a counting plate, and using a phase contrast microscope to track bacterial growth under the effect of different antibiotic concentrations, the results of the minimum inhibitory concentration (MIC) of bacteria under the effect of antibiotics can be obtained in as early as 4 h. We used a combination of E. coli and tigecycline and obtained MIC results that were consistent with those obtained using the gold standard broth micro-dilution method, demonstrating the validity of our method; due to the time advantage, the complete set can be used in the future for point of care and clinical applications, helping physicians to quickly obtain the MIC used to inhibit bacterial growth.

Purpose: The aims of the study were to investigate cellular mechanisms of cold cataract in young lenses of wild-type C57BL/6J (B6WT) mice treated at different temperatures and to test a hypothesis that cold cataract formation is associated with the changes in lens protein and water distribution at different regions across lens fiber cells by Raman spectroscopy (RS).Methods: RS was utilized to scan the mouse lens at different regions with/without cold cataract. Three regions with various opacification along the equatorial axis in the anterior–posterior lens section were scanned. The intensity ratio of Raman bands at 2,935 and 3,390 cm−1 (Ip/Iw) were used to evaluate lens protein and water distribution. We further determined water molecular changes through Gaussian profiles of water Raman spectra.Results: Three specific regions 1, 2, and 3, located at 790–809, 515–534, and 415–434 μm away from the lens center, of postnatal day 14 B6WT lenses, were subjected to RS analysis. At 37°C, all three regions were transparent. At 25°C, only region 3 became opaque, while at 4°C, both regions 2 and 3 showed opacity. The sum of the difference between Ip/Iw and the value of linear fitting line from scattered-line at each scanning point was considered as fluctuation degree (FD) in each region. Among different temperatures, opaque regions showed relatively higher FD values (0.63 and 0.79 for regions 2 and 3, respectively, at 4°C, and 0.53 for region 3 at 25°C), while transparent regions provided lower FD values (less than 0.27). In addition, the decrease in Gaussian peak II and the rising of Gaussian peak III and IV from water Raman spectra indicated the instability of water molecule structure in the regions with cold cataract.Conclusion: Fluctuation degrees of RS data reveal new mechanistic information about cold cataract formation, which is associated with uneven distribution of lens proteins and water across lens fiber cells. It is possible that RS data partly reveals cold temperature-induced redistribution of lens proteins such as intermediate filaments in inner fiber cells. This lens protein redistribution might be related to unstable structure of water molecules according to Gaussian profiles of water RS.

The traditional method of frequency domain weak measurement has a lot of noise. In this paper, we analyze the 2000 curves obtained by experiments and get the conclusion that the signal-to-noise ratio will increase with the increase of signal strength. We simulated the 252 curves produced by the phase change and used this to fit the relationship between the original calculation method and our spectral height ratio (HR) method. Through previous experimental data verification, our method can greatly reduce the system noise of the dual-mode working area in the frequency domain weak measurement. At present, universal frequency domain weak measurement and measurement system have received increasing attention. In this paper, we introduce a frequency domain weak measurement with spectrum height ratio (HR) that can greatly reduce the system noise in the frequency domain weak measurement bimodal work area. Moreover, we completed comparative experiments on a total internal reflection weak measurement system. The experimental results show that the system resolution obtained by using the HR method is 6.33 × 10-7 RIU, which is an order of magnitude higher than that of the conventional center wavelength offset algorithm which is commonly used in weak frequency measurement.

Abstract Background Metabolic dysfunction and neuroinflammation are increasingly implicated in Parkinson’s disease (PD). The pentose phosphate pathway (PPP, a metabolic pathway parallel to glycolysis) converts glucose-6-phosphate into pentoses and generates ribose-5-phosphate and NADPH thereby governing anabolic biosynthesis and redox homeostasis. Brains and immune cells display high activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP. A postmortem study reveals dysregulation of G6PD enzyme in brains of PD patients. However, spatial and temporal changes in activity/expression of G6PD in PD remain undetermined. More importantly, it is unclear how dysfunction of G6PD and the PPP affects neuroinflammation and neurodegeneration in PD. Methods We examined expression/activity of G6PD and its association with microglial activation and dopaminergic neurodegeneration in multiple chronic PD models generated by an intranigral/intraperitoneal injection of LPS, daily subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 6 days, or transgenic expression of A53T α-synuclein. Primary microglia were transfected with G6PD siRNAs and treated with lipopolysaccharide (LPS) to examine effects of G6PD knockdown on microglial activation and death of co-cultured neurons. LPS alone or with G6PD inhibitor(s) was administrated to mouse substantia nigra or midbrain neuron-glia cultures. While histological and biochemical analyses were conducted to examine microglial activation and dopaminergic neurodegeneration in vitro and in vivo, rotarod behavior test was performed to evaluate locomotor impairment in mice. Results Expression and activity of G6PD were elevated in LPS-treated midbrain neuron-glia cultures (an in vitro PD model) and the substantia nigra of four in vivo PD models. Such elevation was positively associated with microglial activation and dopaminergic neurodegeneration. Furthermore, inhibition of G6PD by 6-aminonicotinamide and dehydroepiandrosterone and knockdown of microglial G6PD attenuated LPS-elicited chronic dopaminergic neurodegeneration. Mechanistically, microglia with elevated G6PD activity/expression produced excessive NADPH and provided abundant substrate to over-activated NADPH oxidase (NOX2) leading to production of excessive reactive oxygen species (ROS). Knockdown and inhibition of G6PD ameliorated LPS-triggered production of ROS and activation of NF-кB thereby dampening microglial activation. Conclusions Our findings indicated that G6PD-mediated PPP dysfunction and neuroinflammation exacerbated each other mediating chronic dopaminergic neurodegeneration and locomotor impairment. Insight into metabolic-inflammatory interface suggests that G6PD and NOX2 are potential therapeutic targets for PD.

Redox flow batteries are attractive for large-scale energy storage, but electrode activity should be better understood to improve electrochemical performance. Here the authors map the surface activity distribution of a vanadium redox flow battery electrode with spatial resolution of a single fiber.

The antidisturbance control problem of autonomous vehicle path tracking considering lateral stability is studied in this paper. This paper proposes an improved active disturbance rejection control (IADRC) control method including an improved extended state observer (IESO) and an error compensator based on LQR, where a new continuous nonlinear function is proposed in the IESO instead of the classical piecewise function. Based on the IADRC, an autonomous vehicle path-tracking controller considering lateral stability is designed. Using the output wheel steering angle and external yaw moment, the IESO estimates the disturbance value and compensates for the disturbance in the feedback to meet the goal of antidisturbance control. Based on the concept of control allocation (CA), the control distributor is designed to distribute the external yaw moment to the four wheels in a reasonable and optimal way to achieve differential braking. Finally, the control scheme is evaluated in the form of CarSim/Simulink cosimulation; the results show that the proposed autonomous vehicle path-tracking control scheme has better path-tracking effect and higher antidisturbance robustness.

Infrared neuron stimulation is regarded as an innovative approach for stimulating cochleae in animals while the exact mechanism still remains unknown. In this paper, we studied compound action potentials of guinea pig cochleae with chronic or acute deafness. We recorded optical compound action potentials and analyzed stretched cochlear preparations by fluorescence microscopy. Photoacoustic signals were measured by hydrophone and microphone, respectively. In our experiment, we observed a switch response effect in vitro and in vivo experiments. Therefore, we proposed photoacoustic effect could invoke auditory response in infrared neuron stimulation.

We established a photoacoustic imaging (PAI) system that can provide variable gain at different depths. The PAI system consists of a pulsed laser with an optical parametric oscillator working at a 728nm wavelength and an imaging-acquisition-and-processing unit with an ultrasound transducer. A voltage-controlled attenuator was used to realize variable gain at different depths when acquiring PAI signals. The proof-of-concept imaging results for variable gain at different depths were achieved using specific phantoms. Both resolution and optical contrast obtained through the results of variable gain for a targeted depth range are better than those of constant gain for all depths. To further testify the function, we imaged the sagittal section of the body of in vivo nude mice. In addition, we imaged an absorption sample embedded in a chicken breast tissue, reaching a maximum imaging depth of ∼4.6cm. The results obtained using the proposed method showed better resolution and contrast than when using 50dB gain for all depths. The depth range resolution was ∼1mm, and the maximum imaging depth of our system reached ∼4.6cm. Furthermore, blood vessels can be revealed and targeted depth range can be selected in nude mice imaging.

Background: Infrared laser stimulation has been proposed as an innovative method to elicit an auditory nerve response. Most studies have focused on using long-wavelength infrared (>980nm) pulsed lasers with high water absorption coefficients. This paper sought to assess whether a short-wavelength laser (465nm) with an absorption coefficient as low as 10−3cm−1 would activate the auditory nerve and studied its potential mechanism. Method: Optical compound action potentials (OCAPs) were recorded when synchronous trigger laser pulses stimulate the cochlea before and after deafening, varying the pulse durations (from 800μs to 3600μs) and the amount of radiant energy (from 18.05mJ/cm2 to 107.91mJ/cm2). A thermal infrared imager was applied to monitor the temperature change of the guinea pig cochlea. Results: The results showed that pulsed laser stimulation at 465nm could invoke OCAPs and had a similar waveform compared to the acoustical compound action potentials. The amplitude of OCAPs had a positive correlation with the increasing laser peak power, while the latency of OCAPs showed a negative correlation. The imager data showed that the temperature in the cochlea rose quickly by about 0.3∘C right after stimulating the cochlea and decreased quickly back to the initial temperature as the stimulation ended. Conclusions: This paper demonstrates that 465-nm laser stimulation can successfully induce OCAPs outside the cochlea, and that the amplitude and latency of the invoked OCAPs are highly affected by laser peak power. This paper proposes that a photothermal effect might be the main mechanism for the auditory nerve response induced by short-wavelength laser stimulation.

Self-reference detection is necessary and important to a biosensor. The linear weak measurement system based on total internal reflection has attracted widespread attention due to its high stability, label-free detection, and easy integration. In this paper, we propose a differential detection method based on the linear total internal reflection weak measurement system. We introduce the half-wave plate (HWP) to convert the H light and the V light to each other, thereby obtaining the difference in phase change of the optical path before and after the HWP. Experiments show that the system can not only achieve differential detection, but also has high stability. The linear differential weak measurement system proposed in this paper not only provides a new differential measurement method for real-time biosensors, but also enriches the types of weak measurement sensors.

We propose a self-referential fast detection scheme for a frequency domain weak measurement system for the detection of enantiomeric impurities in chiral molecules. In a transmissive weak measurement system, the optical rotation (OR) is used to modify the pre-selected polarization state and the post-selection polarization state. We obtained the sum and difference of the optical rotations produced by the sample and the standard by rotating the quarter wave plate in the system. Then, we estimate the ratio of chiral molecules to enantiomeric impurities using the ratio of the central wavelength shifts caused by the addition and subtraction states described above. In this paper, our system has an optical resolution of 1.88 × 10−5°. At the same time, we completed the detection of the ratio of the two substances in the mixture of L-proline and D-proline in different proportions, which proved that our system can quickly detect the content of enantiomeric impurities in chiral molecules.

A phase-sensitive fluidic biosensor based on a spectral-domain low-coherence interferometer is presented in this paper. With a fiber optic probe employing the common-path interferometric configuration, subnanometric changes in thickness of the molecular layers can be detected through phase analysis of the acquired interference signal from the sensor surface. Advantages of this biosensor include its picometer-scale thickness sensitivity, 13.9-ms time response, and tolerance to the fluctuation in concentration of the target solution. The capabilities of this biosensor in monitoring specific molecular binding and recognizing specific molecular was successfully demonstrated by using the reactions between the molecules of protein A and IgG. The calculated minimum detectable concentration of IgG is 0.11 µg/mL.