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Rare tumor has a huge unmet medical need without standard regimens, calling for novel therapeutic interventions. The National Cancer Center of China identified a threshold of incidence for rare tumor as 2.5/100,000, based on the characteristics of Chinese population. Molecular profiles for rare tumor patients in China further provided prospects for precise and individualized targeted treatment. An ongoing phase II clinical trial, the PLATFORM study, is the first trial tailored for rare solid tumors in China, featured by molecule‐guided therapeutics. With the promulgation of supportive policies to encourage the development of innovative drugs for rare tumors in China, opportunities will be provided for these patients and the gap will be filled in the treatment of rare tumors.

Synergistic control of the frequency and orbital angular momentum (OAM) of light offers new opportunities for the generation of spatio-temporal optical waveforms and optical metrology. However, their physical realizations are typically bulky and complex owing to challenges in creating, manipulating and detecting mutually coherent, high-dimensional OAM states. Here we achieve combined control over the frequency and the OAM of a comb structure on a photonic chip. Dissipative optical solitons are formed in a nonlinear ring microresonator and emitted owing to engraved angular gratings, with each comb line carrying a distinct OAM. The beam of such a vortex soliton microcomb manifests dynamically revolving, double-helical intensity profiles. The one-to-one correspondence between the OAM and frequencies features a high extinction ratio of over 18.5 dB, enabling precision spectroscopy of optical vortices. Our work provides an integrated solution for realizing coherent light sources that are multiplexed in the spatial and frequency domains, with the potential to establish a new approach to the generation of high-dimensional structured light. Nonlinear microring resonators can generate a vortex soliton microcomb, that is, a frequency comb with each comb line carrying a distinct orbital angular momentum. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia(CA) is defined as a degenerative disease of the nervous system. Repetitive transcranial magnetic stimulation (rTMS) has been a promising treatment for neurological and psychiatric diseases. Hence, to find out whether cerebellar rTMS impacts CA as a potential therapy, we performed a systematic review and meta-analysis. Qualified studies through a systematic search were retrieved for randomized controlled trials (RCTs) using acknowledged databases. Review Manager 5.4 software was employed to synthesize the data. A total of seven studies were identified as eligible and included in the quantitative review. Comparing real and sham-rTMS interventions, the utilization of rTMS on cerebellum improved the scale for the assessment and rating of ataxia (SARA) (SMD − 0.87, 95% CI − 1.41 to − 0.34; P = 0.001; I2 = 62%), the International Cooperative Ataxia Rating Scale (ICARS) (SMD − 1.06, 95% CI − 1.47 to − 0.64; P < 0.00001; I2 = 0%) and Berg balance Scale (BBS) (SMD 0.76, 95% CI 0.33 to 1.19; P = 0.0005; I2 = 39%). The subgroup analysis demonstrated high-frequency of rTMS had a positive effect (SMD − 1.28, 95% CI − 1.82 to − 0.74; P < 0.00001; I2 = 0%). For the safety, the incidence of adverse events between the two groups was not significantly different (OR 1.73, 95% CI 0.55 to 5.46; P = 0.35; I2 = 0%). In conclusion, this meta-analysis provided limited evidence, suggesting a possible strategy that rTMS over the cerebellum could be a viable therapy for symptoms associated with CA. Besides, rTMS intervention was well-attended and did not result in unanticipated negative effects. [ABSTRACT FROM AUTHOR]

Vibrational spectroscopy is a ubiquitous technology that derives the species, constituents and morphology of an object from its natural vibrations. However, natural vibrations of mesoscopic particles—including most biological cells—have remained hidden from existing technologies. These particles are expected to vibrate faintly at megahertz to gigahertz rates, requiring a sensitivity and resolution that are impractical for current optical and piezoelectric spectroscopies. Here we demonstrate the real-time measurement of natural vibrations of single mesoscopic particles using an optical microresonator, extending the reach of vibrational spectroscopy to a different spectral window. Conceptually, a spectrum of vibrational modes of the particles is stimulated photoacoustically by the absorption of laser pulses and acoustically coupled to a high-quality-factor optical resonance for ultrasensitive readout. Experimentally, this scheme is verified by measuring mesoscopic particles with different constituents, sizes and internal structures, showing an unprecedented signal-to-noise ratio of 50 dB and detection bandwidth of over 1 GHz. This technology is further applied for the biomechanical fingerprinting of the species and living states of microorganisms at the single-cell level. This work opens up new avenues to study single-particle mechanical properties in vibrational degrees of freedom and may find applications in photoacoustic sensing and imaging, cavity optomechanics and biomechanics. Natural vibrations of mesoscopic particles, such as living cells, are typically faint; occurring at megahertz to gigahertz frequencies also makes detection challenging. Now, researchers demonstrate real-time measurement of natural vibrations of single mesoscopic particles by using photoacoustic excitation and acoustic coupling to an optical microresonator for readout. [ABSTRACT FROM AUTHOR]

From the perspective of forensic wound age estimation, experiments related to skeletal muscle regeneration after injury have rarely been reported. Here, we examined the time-dependent expression patterns of multiple biomarkers associated with satellite cell fate, including the transcription factor paired box 7 (Pax7), myoblast determination protein (MyoD), myogenin, and insulin-like growth factor (IGF-1), using immunohistochemistry, western blotting, and quantitative real-time PCR in contused skeletal muscle. An animal model of skeletal muscle contusion was established in 30 Sprague–Dawley male rats, and another five rats were employed as non-contused controls. Morphometrically, the data obtained from the numbers of Pax7 + , MyoD + , and myogenin + cells were highly correlated with the wound age. Pax7, MyoD, myogenin, and IGF-1 expression patterns were upregulated after injury at both the mRNA and protein levels. Pax7, MyoD, and myogenin protein expression levels confirmed the results of the morphometrical analysis. Additionally, the relative quantity of IGF-1 protein > 0.92 suggested a wound age of 3 to 7 days. The relative quantity of Pax7 mRNA > 2.44 also suggested a wound age of 3 to 7 days. Relative quantities of Myod1, Myog, and Igf1 mRNA expression > 2.78, > 7.80, or > 3.13, respectively, indicated a wound age of approximately 3 days. In conclusion, the expression levels of Pax7, MyoD, myogenin, and IGF-1 were upregulated in a time-dependent manner during skeletal muscle wound healing, suggesting the potential for using them as candidate biomarkers for wound age estimation in skeletal muscle. [ABSTRACT FROM AUTHOR]

According to previous studies, traditional laboratory safety courses are delivered in a classroom setting where the instructor teaches and the students listen and read the course materials passively. The course content is also uninspiring and dull. Additionally, the teaching period is spread out, which adds to the instructor's workload. As a result, students become less motivated to learn. In contrast, artificially intelligent educational robots (AIERs), help students learn while lessening the workload on instructors by enhancing teaching strategies, using robots to substitute for teachers, giving students access to a variety of instructional content, and improving interaction with students through the use of intelligent voice interactions and Q&A systems to promote student engagement in learning. If the robot is used for a long time for learning, it may lead to a decrease in students' interest in learning. Therefore, this study introduces the GAFCC model (the theory-driven gamification goal, access, feedback, challenge, collaboration design model) as an instructional design model to guide the development of a gamified AIER system, aiming to improve students' motivation and learning effectiveness for laboratory safety courses. To test the effectiveness of the system, this study conducted an experimental study at a university in China in the summer of 2022. 53 participants participated in the research, with a random sample taken from each group. Each participant was able to choose the time of their free time to engage in the experiment. There were 18, 19, and 16 participants in experimental group 1, experimental group 2, and the traditional group, respectively. Students in experimental group 1 learned using the gamified AIER system, students in experimental group 2 learned on a general anthropomorphic robot system and the control group received traditional classroom learning. The experimental results showed that compared to the other two groups, the gamified AIER system guided by the GAFCC model significantly improved students' learning achievement and enhanced their learning motivation, flow experience, and problem-solving tendency. In addition, students who adopted this approach exhibited more positive behaviors and reduced cognitive load in the learning process. [ABSTRACT FROM AUTHOR]

Quantum fluctuations disrupt the cyclic motions of dissipative Kerr solitons (DKSs) in nonlinear optical microresonators and consequently cause timing jitter of the emitted pulse trains. This problem is translated to the performance of several applications that employ DKSs as compact frequency comb sources. Recently, device manufacturing and noise reduction technologies have advanced to unveil the quantum properties of DKSs. Here we investigate the quantum decoherence of DKSs existing in normal-dispersion microresonators known as dark pulses. By virtue of the very large material nonlinearity, we directly observe the quantum decoherence of dark pulses in an AlGaAs-on-insulator microresonator, and the underlying dynamical processes are resolved by injecting stochastic photons into the microresonators. Moreover, phase correlation measurements show that the uniformity of comb spacing of quantum-limited dark pulses is better than 1.2 × 10−16 and 2.5 × 10−13 when normalized to the optical carrier frequencies and repetition frequencies, respectively. Comparing DKSs generated in different material platforms explicitly confirms the advantages of dark pulses over bright solitons in terms of quantum-limited coherence. Our work establishes a critical performance assessment of DKSs, providing guidelines for coherence engineering of chip-scale optical frequency combs. Authors report quantum decoherence of dissipative Kerr solitons in normal-dispersion microresonators, also known as dark pulses. They show the quantum decoherence of dark pulses and their potential advantages over bright solitons in an AlGaAs-on-insulator system. [ABSTRACT FROM AUTHOR]

Special issues are a unique mode of scholarly communication designed to highlight essential or emerging research themes through high-quality manuscripts. Special issues are increasingly becoming a fixture across a wide range of disciplines. Yet whether publishing special issues is necessarily a beneficial practice remains controversial. In this paper, we explore whether the actual effect of special issues meets the academic community's expectations, which is to enhance citation impact and highlight important research topics. Our sample, which comprises all special issue articles in all disciplines published between 2008 and 2017, reveals that there has been a proliferation of special issues across countries, institutions, and journals, with some differences among the disciplines. Opportunities to appear in special issues are more given to countries/institutions that achieved the highest overall research output. The effectiveness of special issues in promoting academic development varies across disciplines and even across journals. Honing in on library and information science as a case area to explore citation impacts and the topic distribution of special issues, we find that many special issues present high-impact manuscripts, especially those of the less prominent journals. However, the issue of publishing low impact manuscripts through special issues also exists in many fields. Special issues are also more likely to publish interdisciplinary or cross-disciplinary articles and rarely discussed research themes compared to regular issues. Further, such topics are seldom explored on a large scale in the normal editions of the journal. To ensure the quality of the manuscripts, we recommend optimizing the procedures for selecting special issue topics and reviewing submissions. [ABSTRACT FROM AUTHOR]

Optical microresonators with high quality (Q) factors are essential to a wide range of integrated photonic devices. Steady efforts have been directed towards increasing microresonator Q factors across a variety of platforms. With success in reducing microfabrication process-related optical loss as a limitation of Q, the ultimate attainable Q, as determined solely by the constituent microresonator material absorption, has come into focus. Here, we report measurements of the material-limited Q factors in several photonic material platforms. High-Q microresonators are fabricated from thin films of SiO2, Si3N4, Al0.2Ga0.8As, and Ta2O5. By using cavity-enhanced photothermal spectroscopy, the material-limited Q is determined. The method simultaneously measures the Kerr nonlinearity in each material and reveals how material nonlinearity and ultimate Q vary in a complementary fashion across photonic materials. Besides guiding microresonator design and material development in four material platforms, the results help establish performance limits in future photonic integrated systems. Optical absorption and nonlinear index are important performance drivers in devices like microcombs. Here the authors use resonance-enhanced nonlinear spectroscopy to characterize absorption limits and nonlinear index for some integrated photonic materials. [ABSTRACT FROM AUTHOR]

The genus Bambusa belongs to the subtribe Bambusinae and the subfamily Bambusoideae. The subgenera of Bambusa has not been satisfactorily circumscribed, and this remains a major taxonomic issue. Simultaneously, genera such as Dendrocalamus and Gigantochloa have not been confidently assigned to Bambusa. Here, the phylogenetic relationships among subgenera were investigated using five chloroplast DNA markers (rpl32-trnL, rpl16, matK, rbcL, and trnH-psbA) for a sample of 50 ingroup and 16 outgroup species. A total of 186 key morphological descriptors were studied for the 50 ingroup species. The results indicated that five chloroplast DNA markers were possible to distinguish Bambusa species from other species and divide them into several clusters. Phylogenetic analyses conducted using morphological descriptors and a combined marker (rpl32-trnL+rpl16) revealed three and five distinct lineages, respectively, among the currently recognized Bambusa species. The branching pattern of the dendrogram was not completely consistent with the classical taxonomic classification of Bambusa. In addition, not all varieties and cultivars were clustered with McClure classifications. As the maximum parsimony topology and morphological analyses were inconsistent, some clustering results overlapped. Overall, the results obtained here do not support the current classification of the Bambusa subgenera. [ABSTRACT FROM AUTHOR]

We investigated oxidative stress and antioxidant response in the p62/Sqstm1-Keap1-Nrf2 pathway in C57BL/6 mice cochleae during age-related hearing loss (ARHL) and noise-induced hearing loss (NIHL), and the function of full-length and variant p62 in the regulation of Nrf2 activation. Groups of young (2 months), old (13–14 months), control, and acoustic trauma (AT) mice were examined cochlear damage and oxidative stress as follows: auditory brainstem response and hair cell counts; malondialdehyde (MDA) levels measured by assay kit and 7,8-dihydro-8-oxoguanine (8-oxoG) detected by immunohistochemistry. Full-length and variant p62 were examined for expression in cochleae, hippocampus (HIP), and auditory cortex (AC) using immunoblotting. Keap1-Nrf2 pathway activation was based on immunoblotting of nuclear Nrf2 and quantitative real-time PCR of Nrf2 target genes HO-1/NQO-1. The oxidative function of full-length and variant p62 was examined in HEI-OC-1 cells by flow cytometry. The results showed hearing loss, and cochlear hair cell loss was associated with MDA accumulation and 8-oxoG expression during ARHL and NIHL. Nrf2 showed no obvious changes in nuclear protein. Expression levels mRNA for HO-1 and NQO1 were lower in old mice and mildly greater in AT Mice. The expression of p62 splicing variant lacking the Keap1-interacting region was greater than full-length p62 in cochleae. However, the expression of p62 splicing variant was lesser than full-length p62 in HIP and AC. For HEI-OC-1 cells, overexpression of full-length p62 decreased ROS levels induced by H2O2. Oxidative stress is closely related to ARHL and NIHL. Changing the ratio of full-length to variant p62 protein expression may be a new target to reduce the level of oxidative stress in cochleae. [ABSTRACT FROM AUTHOR]

In poultry, feed restriction is common feeding management to limit poultry nutrients intake so that poultry only intake the essential energy, meeting the basic need of growth and development. Our study investigated whether feeding restriction affects the diversity of the intestinal microbiota of growing breeding ducks. In this research, the 60–120-day-old ducks were raised in restricted and free-feeding groups. After slaughtering, the carcass traits and the cecal contents were collected for 16S rRNA sequencing analysis. After feeding restriction, the growth rate of ducks was limited, the weight and rate of abdominal fat decreased, and the rate of chest and leg muscles increased. In addition, feeding restriction can also change the diversity of intestinal microorganisms in breeding ducks, such as the increase of Firmicutes abundance and the decrease of Bacteroidetes abundance. After analyzing of correlation, significant correlations between gut microbiota and carcass phenotypes were found. The results indicated that gut microbiota might be involved in the life activities associated with phenotypic changes. This study proved the effect of feeding methods on the intestinal microbiota of ducks, providing a theoretical basis of the microbial angle for raising ducks in a feeding-restricted period. [ABSTRACT FROM AUTHOR]

It is widely recognized that flipped learning has great potential for enhancing students' conceptual understanding through the reversed arrangement of before-class learning activities and in-class settings. However, this approach also raises the challenge of students having to obtain the learning content by themselves, especially for abstract concepts such as fractions, where students frequently encounter problems in mathematics education. In this study, we proposed a gamified interactive e-book approach to supporting a flipped mathematics classroom. To evaluate the effectiveness of the proposed approach, a quasi-experimental study was implemented in an elementary school mathematics course. There were three groups: the students who adopted the gamified interactive e-book in the mathematical flipped classroom (the GIEBFL group), the students who learned with conventional flipped learning (the CFL group), and those who learned with traditional instruction (the TI group). The results from a paper-and-pencil test indicated that the GIEBFL students significantly outperformed the CFL and TI students. In addition, the questionnaire of students' learning motivation showed that the GIEBFL students had better motivation than the CFL and TI students. Also, the GIEBFL students achieved significantly higher meta-cognition tendency than the TI students. [ABSTRACT FROM AUTHOR]

Silicon nitride (SiN) waveguides with ultra-low optical loss enable integrated photonic applications including low noise, narrow linewidth lasers, chip-scale nonlinear photonics, and microwave photonics. Lasers are key components to SiN photonic integrated circuits (PICs), but are difficult to fully integrate with low-index SiN waveguides due to their large mismatch with the high-index III-V gain materials. The recent demonstration of multilayer heterogeneous integration provides a practical solution and enabled the first-generation of lasers fully integrated with SiN waveguides. However, a laser with high device yield and high output power at telecommunication wavelengths, where photonics applications are clustered, is still missing, hindered by large mode transition loss, non-optimized cavity design, and a complicated fabrication process. Here, we report high-performance lasers on SiN with tens of milliwatts output power through the SiN waveguide and sub-kHz fundamental linewidth, addressing all the aforementioned issues. We also show Hertz-level fundamental linewidth lasers are achievable with the developed integration techniques. These lasers, together with high-Q SiN resonators, mark a milestone towards a fully integrated low-noise silicon nitride photonics platform. This laser should find potential applications in LIDAR, microwave photonics and coherent optical communications. Achieving high output power and low noise integrated lasers is a major challenge. Here the authors experimentally demonstrate integrated lasers from a Si/SiN heterogeneous platform that shows Hertz-level linewidth, paving the way toward fully integrating low-noise silicon nitride photonics in volume using real devices for lasing. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1038/s41566-021-00805-y. [ABSTRACT FROM AUTHOR]