An ATMND/SGI based three-way junction ratiometric fluorescent probe for rapid and sensitive detection of bleomycin.

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket. The unique "Y" structure not only could entrap ATMND in the mismatch pocket with high affinity, leading to FL quenching at 408 nm, but also embed SGI in the grooves of the double-stranded portion, resulting in FL enhancement at 530 nm. In the presence of BLM-Fe(II), the "Y" structure of D6 was destroyed due to the specific cleavage of the BLM recognition site, the 5'-GT-3' site in D6. This caused the release of ATMND and SGI and thus the ratiometric signal change of FL enhancement by ATMND and FL quenching by SGI. Under optimal conditions, the ratiometric probe exhibited a linear correlation between the intensity ratio of F408/F530 and the concentration of BLM in the range of 0.5-1000 nM, with a detection limit of 0.2 nM. In addition, the probe was applied to detect BLM in human serum samples with satisfactory results, indicating its good clinical application potential.

Spatially confined dual-emission nanoprobes assembled from silicon nanoparticles and gold nanoclusters for ratiometric biosensing.

Gold nanoclusters (AuNCs) possess weak intrinsic fluorescence, limiting their sensitivity in biosensing applications. This study addresses these limitations by developing a spatially confined dual-emission nanoprobe composed of silicon nanoparticles (SiNPs) and AuNCs. This amplified and stabilized fluorescence mechanism overcomes the limitations associated with using AuNCs alone, achieving superior sensitivity in the sensing platform. The nanoprobe was successfully employed for ratiometric detection of bleomycin (BLM) in serum samples, operating at an excitation wavelength of 365 nm, with emission wavelengths at 480 nm and 580 nm. The analytical performance of the system is distinguished by a linear detection range of 0-3.5 µM, an impressive limit of detection (LOD) of 35.27 nM, and exceptional recoveries ranging from 96.80 to 105.9%. This innovative approach significantly enhances the applicability and reliability of AuNC-based biosensing in complex biological media, highlighting its superior analytical capabilities.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold CmiR-21 > CmiR-892b, the CAR-CHA-HCR circuit performs a compute-and-release operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

Ratiometric fluorescence determination of alkaline phosphatase activity based on carbon dots and Ce3+-crosslinked copper nanoclusters.

A new ratiometric fluorescent probe for efficient determination of ALP was developed. The probe was constructed by combining Ce3+-crosslinked copper nanoclusters (Ce3+-CuNCs) which exhibit the aggregation-induced emission (AIE) feature with carbon dots (CDs). The introduction of phosphate (Pi) induced the generation of CePO4 precipitation, resulting in significant decrease of fluorescence emission of CuNCs at 634 nm. At the same time, the fluorescence of CDs at 455 nm was obviously enhanced, thus generating ratiometric fluorescence response. Based on the fact that the hydrolysis of pyrophosphate (PPi) by ALP can produce Pi, the CD/Ce3+-CuNCs ratiometric probe was successfully used to determine ALP. A good linear relationship between the ratiometric value of F455/F634 and ALP concentrations ranging from 0.2 to 80 U·L- 1 was obtained, with a low detection limit of 0.1 U·L- 1. The ratiometric responses of the probe resulted in the visible fluorescence color change from orange red to blue with the increase of ALP concentration. The smartphone-based RGB recognition of the fluorescent sample images was used for ALP quantitative determination. A novel ratiometric fluorescent system based on Ce3+-CuNCs with AIE feature and CDs were constructed for efficient detection of ALP.

Entanglement Purification for Logic-Qubit of Photon System Based on Parity Check Measurement Gate.

It has been found that logic-qubit entanglement has great potential for applications in quantum communication and quantum networks in recent years. However, along with the effects of noise and decoherence, the fidelity of the communication transmission can be greatly reduced. In this paper, we investigate the entanglement purification of logic bit-flip error and phase-flip error in polarization logic-qubit entanglement based on the parity-check measurement (PCM) gate, which is constructed by the cross-Kerr nonlinearity and used to distinguish the parity information of two-photon polarization states. The probability of entanglement purification is higher than the scheme using the linear optical method. Moreover, the quality of logic-qubit entangled states can be improved by a cyclic purification process. This entanglement purification protocol will be useful in the future when faced with long-distance communication with logic-qubit entanglement states.

Decomposition-based multiobjective optimization for multipass cell design aided by particle swarm optimization and the K-means algorithm.

We proposed a method to intelligently design two-spherical-mirror-based multipass cells (MPCs) and optimize multiple objectives simultaneously. By integrating the K-means algorithm into the particle swarm optimization (PSO) algorithm, an efficient method is developed to optimize MPC configurations possessing characteristics of both long optical path lengths (OPLs) and circle patterns. We built and tested an MPC with four concentric circle patterns, which achieved an OPL of 54.1 m in a volume of 273.1 cm3. We demonstrated the stability and detection precision of the developed gas sensor. Continuous measurement of methane in ambient laboratory air was realized, with a detection precision of 8 ppb and an averaging time of 13 s. The combination of K-means and PSO algorithms is effective in optimizing MPCs with multiple objectives, which makes it suitable for designing versatile MPCs satisfying various requirements of field applications, including pollution and greenhouse gas emission monitoring and high-sensitivity measurements of other trace gases.

Optical design of Lissajous pattern multipass cells with multiple spherical mirrors based on particle swarm optimization.

We propose a method to intelligently design and optimize a multiple-spherical-mirror-based multipass cell (MPC) with Lissajous patterns. The MPC consists of at least three spherical mirrors, which are placed in a rotationally symmetric arrangement. Particle swarm optimization (PSO) is performed to optimize the parameters of the MPC configurations and accelerate the design process. Two Lissajous patterned MPCs with three and five mirrors are built and tested experimentally. We further develop an open-path gas sensor based on a five-mirror-based MPC to detect methane concentrations in ambient laboratory air, and a detection precision of 1.1 ppb with a 123 s averaging time is realized. The PSO algorithm is efficient for optimizing the proposed MPC, which has superior proprieties of symmetry configuration, cost-effectiveness and high detection sensitivity and is well suited for trace gas sensing applications.

Long-wavelength emission carbon dots as self-ratiometric fluorescent nanoprobe for sensitive determination of Zn2.

A novel ratiometric fluorescence nanoprobe based on long-wavelength emission carbon dots (CDs) was designed for high sensitive and selective detection of Zn2+. The CDs were conveniently prepared by a one-step solvothermal treatment of formamide and glutathione (GSH). Under single excitation wavelength (420 nm), the obtained CDs exhibit three emission peaks at 470, 650, and 685 nm, respectively. For the long-wavelength emission region of the CDs, the fluorescence at 685 nm can be quenched with different levels upon the addition of most metal ions. However, the presence of Zn2+ not only results in the fluorescence quenching at 685 nm effectively but also enhances at 650 nm remarkably, which may be due to the formation of CD-Zn2+ chelate complex inducing the dispersion of CDs aggregates and changes in the group distribution on the surface of CDs. Taking the advantage of the unique fluorescence response induced by Zn2+, the prepared CDs were successfully employed as nanoprobe for self-ratiometric fluorescence determination of Zn2+ with F650/F685 as signal output. A good linear relationship in the concentration range 0.01 to 2 µM, and a detection limit as low as 5.1 nM has been obtained. The ratiometric nanoprobe was successfully applied to  Zn2+ determination  in human serum samples.

Subjective and objective risk perceptions and the willingness to pay for agricultural insurance: evidence from an in-the-field choice experiment in rural China.

We conducted in-the-field choice experiments in China to investigate farmers' willingness to pay for crop insurance and to determine how objective and subjective beliefs affect Willingness to Pay (WTP). We deploy three variants of the choice experiment using a priming mechanism on objective and subjective beliefs plus a control. We find that the cuing frame matters in that there are differences in WTP within five attributes and across variants. In terms of practical policy, our results suggest that farmers' frame of reference toward objective and subjective risks can affect insurance demand.

Naphthalimide Derivative-Functionalized Metal-Organic Framework for Highly Sensitive and Selective Determination of Aldehyde by Space Confinement-Induced Sensitivity Enhancement Effect.

Facile and sensitive determination of formaldehyde (FA) in indoor environments still remains challenging. Herein, a fluorescent probe, termed PHN@MOF, was synthesized by embedding the fluorescent molecule of N-propyl-4-hydrazine-naphthalimide (PHN) into a metal-organic framework (MOF) for sensitive and visual monitoring of FA. The hydrazine group of PHN acts as the specific reaction group with FA based on the condensation reaction. The host of MOF (UiO-66-NH2) offers the surrounding confinement space required for the reaction. Owing to the enrichment effect and molecular sieve selection of UiO-66-NH2 to FA, PHN@MOF, compared with free PHN, exhibits very high sensitivity and selectivity based on space confinement-induced sensitivity enhancement (SCISE). Moreover, the fluorescence of UiO-66-NH2 offers a reference signal for FA detection. Using this ratiometric fluorescent PHN@MOF probe, a colorimetric gel plate and test paper were developed and used to visually monitor FA in air.

Generalized optical design and optimization of multipass cells with independent circle patterns based on the Monte Carlo and Nelder-Mead simplex algorithms.

In this paper, we propose an automatic approach to optimize the multipass cell (MPC) design with independent circle patterns. First, the Monte Carlo algorithm is performed to globally search for the characteristic values of the distance between two mirrors. Second, the Nelder-Mead simplex (NM) algorithm is applied to locally optimize the re-entry condition. In addition, we utilize the clustering method to select the independent circle patterns automatically. Three optimal MPCs with five, seven and nine independent circles are built and tested experimentally. We analyze the stability of the final point for the MPCs and optimize the quality of the output beam based on multi-ray tracing. This type of MPC shows the superior characteristics of compactness, high detection sensitivity, and affordability, has various applications, and can promote the development of portable gas sensors. The proposed approach is effective and efficient for automatically optimizing MPC design and can be further extended to versatile optical designs.

A carbon dot doped lanthanide coordination polymer nanocomposite as the ratiometric fluorescent probe for the sensitive detection of alkaline phosphatase activity.

The development of sensitive methods for alkaline phosphatase (ALP) activity analysis is an important analytical topic. Based on the stimulus-responsive lanthanide coordination polymer, a simple ratiometric fluorescence sensing strategy was proposed to detect ALP activity. A carbon dot (CD) doped fluorescent supramolecular lanthanide coordination polymer (CDs@Tb-GMP) was prepared with Tb3+ and the ligand guanine single nucleotide (GMP). To construct a ratiometric fluorescence biosensor, the fluorescence of Tb-GMP was used as a response signal, and the fluorescence of CDs was used as a reference signal due to its good stability. When excited at 290 nm, the polymer network Tb-GMP emits characteristic fluorescence at 545 nm, while the CDs encapsulated in the polymer network emit fluorescence at 370 nm. After adding ALP to the system, the substrate GMP can be hydrolyzed by ALP, resulting in the destruction of the polymer network. Accordingly, the fluorescence of Tb-GMP significantly decreased, while the fluorescence of CDs slightly increased due to their release from the polymer network. By comparing the relationship between the fluorescence intensity ratio of the two signals and the concentration of ALP, sensitive detection of ALP could be achieved with the linear range from 0.5 to 80 U L-1 and a detection limit of 0.13 U L-1. Furthermore, the proposed ratiometric sensing system was applied to the detection of ALP in human serum samples with desirable results, indicating potential application in clinical diagnosis.

Occupational hazards, health costs, and pesticide handling practices among vegetable growers in Pakistan.

Disregarding protective measures when handling pesticides in agricultural production imposes increased health risks and health costs on farmers as well as degrades the natural ecosystem. In Pakistan, where agriculture is the prime occupation in rural communities, there is overwhelming evidence of indiscriminate use of hazardous pesticides by farmers without taking adequate precautions. Using cross-sectional data, we examined personal protection and health costs to vegetable growers due to pesticide exposure and determinants of farmers' pesticide handling practices. The theory of averting behavior was used, and the possible factors affecting farmers' adoption of safety equipment and of disposal methods for pesticide containers were estimated using a logit model. Health effects (P < 0.05) and farmers' protection and health costs (P < 0.01) are found as important determinants of farmers' adoption of safety equipment and of disposal methods for pesticide containers. The mean protection and health cost of pesticide exposure per farmer per vegetable season in 2019 was US $3.60. Analytical outcomes indicate that safe and recommended pesticide handling practices are needed to be introduced through adequate integrated pest management (IPM) training programs and by improving farmers' formal education. Thus, creating awareness through IPM training programs among vegetable growers and enhancing formal education to encourage the adoption of precautionary measures and safe disposal methods for pesticide containers may reduce health risks and health costs. Findings imply that adoption of adequate pesticide handling practices would further help reduce occupational hazards and promote sustainable agriculture in Pakistan.

A novel ratiometric fluorescence nanoprobe for sensitive determination of uric acid based on CD@ZIF-CuNC nanocomposites.

A novel ratiometric fluorescence nanoprobe based on carbon dots (CDs) and Cu nanoclusters (CuNCs) was designed for the label-free determination of uric acid (UA). The metal-organic framework (MOF) encapsulated CuNCs (ZIF-CuNC), and nitrogen-doped CDs can self-assemble into well-defined spherical nanocomposites (CD@ZIF-CuNC) due to physical adsorption. Under the excitation wavelength of 360 nm, the CD@ZIF-CuNC nanocomposites exhibit two evident intrinsic emissions peaked at 460 nm (CDs) and 620 nm (ZIF-CuNC), respectively. In the presence of H2O2, the fluorescence of CD@ZIF-CuNC at 620 nm is quenched remarkably within 1 min, while little effect on the emission at 460 nm is observed. Therefore, taking the fluorescence at 620 nm as the report signal and 460 nm as the reference signal, ratiometric quantitative determination of H2O2 was achieved with a linear range of 1-100 µM and a detection limit of 0.30 µM. The CD@ZIF-CuNC nanoprobe was successfully applied to the determination of UA that is catalyzed by uricase to produce H2O2, obtaining the linear range of 1-30 µM and the detection limit of 0.33 µM. Eventually, this strategy has been successfully applied to the determination of UA in human urine samples. A novel and convenient CDs@ZIF-CuNCs-based nanoplatform was constructed for sensitive ratiometric fluorescence determination of UA.

Bioenergy consumption, carbon emissions, and agricultural bioeconomic growth: A systematic approach to carbon neutrality in China.

China is the world's largest fossil fuel consumer and carbon emitter country. In September 2020, China pledged to reduce carbon emissions, and achieve carbon neutrality by 2060. Therefore, this study aimed to contribute to the literature and show the pictorial nexus of bioenergy and fossil fuel consumption, carbon emission, and agricultural bioeconomic growth, a new pathway towards carbon neutrality. For this study, time-series data from 1971 to 2019 were used to analyze the autoregressive distributed lag (ARDL) bound testing and novel dynamic autoregressive distributed lag (DYNARDL) simulation models. Initially, the unit root tests results showed that all variables were stationarity at the level and first difference. The presence of cointegration between selected variables was confirmed by the results from ARDL bound test. In addition, the results of long-run and short-run nexus show an increase in bioenergy consumption that caused an increase in agricultural bioeconomic growth both in the long and short-run nexus. A decrease in fossil fuel consumption was shown to result in increased agricultural bioeconomic growth with respect to both long- and short-term effects. Furthermore, the results of the novel dynamic ARDL simulation model demonstrated that a 10% positive shock from bioenergy consumption caused an increase in agricultural bioeconomic growth, while at the same time, a 10% negative shock in bioenergy consumption led to a decrease. A 10% negative shock from fossil fuels caused an increase in agricultural bioeconomic growth, whereas a 10% positive shock from fossil fuels led to a decrease. Therefore, this study suggests that China needs to switch from fossil fuel and other non-renewable energy consumption to sources of bioenergy and other renewable energy consumption to achieve carbon neutrality by 2060.

A Boric Acid-Functionalized Lanthanide Metal-Organic Framework as a Fluorescence "Turn-on" Probe for Selective Monitoring of Hg2+ and CH3Hg.

Mercury detection remains an important task because of its high toxicity. Herein a new dual-signal probe based on a boric acid (BA)-functionalized lanthanide metal-organic framework (BA-Eu-MOF) was developed for the detection of Hg2+ and CH3Hg+ ions for the first time. The BA-Eu-MOF was synthesized by coordination of Eu3+ with 5-boronobezene-1, 3-dicarboxylic acid (5-bop) through a one-pot method. The 5-bop ligand not only acted as the "antenna" to sensitize the luminescence of Eu3+ but also provided reaction sites for Hg2+ and CH3Hg+. Owing to the electron-withdrawing effect of the BA group, the "antenna" effect of the ligand was passivating and the BA-Eu-MOF showed weak red emission in water. Upon addition of Hg2+ or CH3Hg+ into the system, a transmetalation reaction took place, i.e., BA groups were replaced by Hg2+ or CH3Hg+; therefore, the "antenna" effect of the ligand was triggered, leading to the enhancement of red emission. As Hg2+ or CH3Hg+ concentration increased, the red emission was gradually enhanced, and the color change was also observed with the naked eye under 365 nm ultraviolet light. Owing to the porous characteristics and the surface effect of the MOF, as well as the unique transmetalation reaction between the BA group and Hg2+ or CH3Hg+, the developed nanoprobe showed excellent characteristics for simultaneous detection of Hg2+ and CH3Hg+, such as simple preparation, convenient operation, "turn-on" signal output, high sensitivity, and selectivity. The unique features of the BA-Eu-MOF make it an attractive probe for monitoring Hg2+ and CH3Hg+.

Fluorescent and colorimetric determination of glutathione based on the inner filter effect between silica nanoparticle-gold nanocluster nanocomposites and oxidized 3,3',5,5'-tetramethylbenzidine.

Determination of glutathione (GSH) is closely related to the clinical diagnosis of many diseases. Thus, a fluorescent and colorimetric dual-readout strategy for the sensitive determination of glutathione was proposed. The mesoporous silica nanoparticle-gold nanocluster (MSN-AuNC) nanocomposites with significantly enhanced emission and effectively improved photostability characteristics were used as fluorescent probes. Based on the inner filter effect (IFE), the fluorescence of MSN-AuNCs at 570 nm can be effectively quenched by oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) with absorption in the wavelength ranges of 330-470 nm and 500-750 nm. However, the addition of GSH could cause the reduction of blue oxTMB to colorless TMB, resulting in the inhibition of IFE and the recovery of the fluorescence of MSN-AuNCs. Therefore, using oxTMB as both quencher and color indicator, a dual-readout oxTMB/MSN-AuNC sensing system for the sensitive determination of GSH was constructed. As signal amplification is caused by the fluorescence enhancement of MSN-AuNCs, the detection limits as low as 0.12 µM and 0.34 µM can be obtained for fluorescent and colorimetric assay, respectively. This method may not only offer a new idea for the sensitive and effective determination of GSH, but also broaden the applications of AuNCs in fluorescent and colorimetric dual-readout bioanalysis.

Optical design and analysis of a two-spherical-mirror-based multipass cell.

A systematic method for the optical design and analysis of a multipass cell (MPC) with two spherical mirrors is presented. By varying the parameters, including the distance between the mirrors, the position of the incident point, and the incident angles, a variety of dense patterns can be formed on the mirrors. Three MPCs with exemplary patterns of seven circles, rotating triangles, and petals are designed and built. We compare and analyze the parameters of each MPC with respect to the volume, the optical path length (OPL), the number of reflections, and the stability of the final spot position. This new type of MPC exhibits the superior characteristics of compactness, a long effective OPL, and affordable cost, which make it very suitable for applications to trace gas sensing.

Photoelectrochemical determination of trypsin by using an indium tin oxide electrode modified with a composite prepared from MoS2 nanosheets and TiO2 nanorods.

A photoelectrochemical (PEC) method has been developed for sensitive detection of trypsin. It is based on the use of a composite consisting of MoS2 nanosheets and TiO2 nanorods (MoS2-TiO2). The material has a high specific surface area, superior electrical conductivity, excellent biocompatibility and good band gap matching. The composite was synthesized by a one-pot method using TiO2 as a template. This results in a uniform distribution of the MoS2 nanosheets (<5 layers) in the composite. If the composite, placed on an indium tin oxide (ITO) electrode, is coupled to apoferritin, the photocurrent response decreases due to the insulating effect of the protein. Trypsin, in acting as an alkaline protease, decomposes the apoferritin. This results in the recovery of the PEC signal. Attractive features of this PEC method include (a) a superior PEC signal, (b) sensor stability, (c) simple operation, and (d) the lack of any additional modifications of the biosensor. This warrants high sensitivity, reproducibility, repeatability and practicality. The ITO sensor has a linear response in the 1 to 1000 ng·mL-1 trypsin concentration range and a 0.82 ng·mL-1 detection limit. The assay was applied to the determination of trypsin in spiked serum samples and gave satisfactory results. Graphical abstract Schematic presentation of an indium tin oxide (ITO)/MoS2-TiO2 sensor for detecting trypsin. The PEC signal was decreased after immobilization of apoferritin (APO) on the modified ITO. Trypsin catalytically hydrolyzes APO specifically and induces the PEC signal to recover.

Can trastuzumab emtansine be replaced by additional chemotherapy plus targeted therapy for HER2-overexpressing breast cancer patients with residual disease after neoadjuvant chemotherapy?

Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis, and can easily metastasize and recur. Currently, chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients. Given that neoadjuvant chemotherapy (NAC) has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits, many patients, especially those with more advanced tumors, prefer NAC and generally will not receive additional chemotherapy after surgery, irrespective of the pathological response. However, achieving pathological complete response to NAC is strongly correlated with prognosis, especially in triple-negative and HER2-overexpressing breast cancer. Therefore, postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes. The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC. In addition, chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions. Therefore, can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer? At present, no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer. The KATHERINE study revealed that trastuzumab emtansine (T-DM1) can reduce the risk of recurrence or death by 50% compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy. T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine, and thus, to an extent, T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy. However, high cost and low accessibility limit its use especially in low- and middle-income countries and regions. Hence, we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1. Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable. However, further clinical research on the selection of chemotherapeutic agents is warranted.